Cancer Support 2009

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Cancer Support
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Sponsored by
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2009
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Cancer Support 2009

Introduction 4 Chemotherapy-Induced Diarrhea:
Melvin E. Liter, MS, PharmD
Treatment Guidelines 106
Liter Consulting Services Updated for 2009 by
Liter Enterprises, LLC
Lexington, Kentucky Tyra Gatewood, PharmD, BCOP
Clinical Pharmacist
Parenteral Therapeutic Agents for Cancer 7
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H. Lee Moffitt Cancer Center & Research Institute
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Tampa, Florida
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Val R. Adams, PharmD, FCCP, BCOP Text originally developed by
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Associate Professor
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Scott Wadler, MD (deceased)
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University of Kentucky College of Pharmacy
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Lexington, Kentucky Richard T. Silver Professor of Hematology and Oncology
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Head, Solid Tumor Service
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Safe Handling of Hazardous Drugs
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Weill Medical College of Cornell University
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New York, New York
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Martha Polovich, MN, RN, AOCN
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Associate Director of Clinical Practice
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Duke Oncology Network
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Durham, North Carolina
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Luci A. Power, MS, RPh
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Senior Consultant
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Power Enterprises
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San Francisco, California
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Chemotherapy-Induced Nausea and Vomiting:
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Treatment Guidelines
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David G. Frame, PharmD
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Clinical Assistant Professor of Pharmacy
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College of Pharmacy
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University of Michigan
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Clinical Pharmacist DISCLAIMER—This pocket guide is designed to be a summary of information. While
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University of Michigan Hospital it is detailed, it is not an exhaustive pharmaceutical review; the entries in this publica-
Ann Arbor, Michigan tion present selected facts about each product. McMahon Publishing, the authors,
and Teva Pharmaceuticals USA assume no liability for the use of this guide, and the
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William Leslie, MD accuracy of the information contained herein is not guaranteed. Readers are strongly
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urged to consult any relevant primary literature and the complete prescribing infor-
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Assistant Professor of Medicine
mation available in the package insert of each drug and appropriate clinical protocols.
Rush Medical College Copyright © 2008, McMahon Publishing, 545 West 45th Street, New York, NY 10036.
Rush University Printed in the USA. All rights reserved, including the right of reproduction, in whole or
Chicago, Illinois in part, in any form.
2 Cancer Support 2009 Cancer Support 2009 3

administration process.
Introduction Health care workers are exposed throughout the life
cycle of the drug distribution process. This process includes
Melvin E. Liter, MS, PharmD the manufacture, transportation, distribution, administra-
Liter Consulting Services
tion, and disposal of drugs. Some of the more common
Liter Enterprises, LLC
Lexington, Kentucky forms of exposure occur through dermal contact, inhala-
tion, and ingestion. The risk for exposure can be increased
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ancer is the second leading cause of death in the from inadvertent surface contamination and incomplete
United States (22.8% of all deaths), surpassed only decontamination of the workplace. It is estimated that the
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by heart disease. The lifetime probability of devel- number of health care workers who may be exposed to
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hazardous drugs exceeds 5.5 million.4
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oping cancer of any type is 1 in 2 for men and 1 in 3 for
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women. In 2008, it is estimated that 1,437,180 new cases In an endeavor to improve safety for health care workers
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of cancer will be diagnosed in the United States and that who may become exposed to cancer therapeutic agents,
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approximately 565,650 Americans (more than 1,550 per this pocket guide lists available parenteral cancer thera-
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day) will die of the disease.1 peutic agents and provides important information about
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Cancer develops as a result of physiologic changes asso- the drugs listed, including indications, dose ranges, spe-
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ciated with advancing age, lifestyle changes, environmen- cial instructions, toxicities, boxed warnings, extravasation
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tal exposure, and heredity. Tobacco use, poor nutrition, categories (ie, vesicant, irritant, or nonirritant), and haz-
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inactivity, and obesity are preventable causes of cancer in ardous drug information.
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the United States. According to John R. Seffrin, PhD, chief The safe handling of hazardous drugs is important to
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executive officer of the American Cancer Society, “Tobacco health care workers from the beginning to the end of the
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is already the single greatest cause of preventable death exposure period and especially during the compounding
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in the world. If current trends continue, 500 million people and administration processes. In an effort to promote safe-
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alive today will eventually die prematurely and needlessly ty, this guide outlines characteristics of hazardous drugs,
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from tobacco-related disease.”2 Current patterns of weight detrimental effects of occupational exposure, methods of
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gain and obesity in the United States can account for cancer determining exposure, and common routes of exposure. The
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deaths in 1 in 7 men and 1 in 5 women. Many other cancer guide also highlights the technologies available to reduce
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deaths could be prevented by greater utilization of avail- risks and national guidelines for ensuring safe compound-
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able screening tests.3 ing, transport, delivery, administration, and disposal of haz-
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The reality of cancer is that it affects not only the ardous drugs by using personal protective equipment.
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patients but also everyone involved with those patients, Chemotherapy-induced nausea and vomiting (CINV) is a
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including their family members. Cancer is not contagious, significant complication associated with cancer treatment.
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but it causes physical and mental trauma to all who come Before the advent of current treatment choices, nausea and
in contact with it, and the treatment of cancer introduces vomiting resulted in patients refusing therapy. Today, very
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risks to both patients and health care providers. few patients refuse therapy from fear of nausea and vomit-
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Drugs used to treat cancer are both beneficial and haz- ing. However, significant numbers of patients are inade-
ardous in that they can both destroy the disease and cause quately treated, even with the availability of improved anti-
the disease. Many cancer therapeutic agents are carci- emetic therapy. The section of this pocket guide on nausea
nogenic and represent a safe-handling risk to clinicians. and vomiting provides an educational foundation to assist
Several chemotherapeutic agents are vesicants and can in a better understanding of the mechanisms of nausea and
cause severe damage to patients if infiltrated during the vomiting and a basis for more aggressive treatment with

newly approved treatment options. The guidelines in this sec-

tion summarize the most updated Multinational Association
Parenteral Therapeutic
of Supportive Care in Cancer panel’s recommendations. Agents for Cancer
Chemotherapy-induced diarrhea (CID) is a significant
dose-limiting toxicity associated with chemotherapy. It Val R. Adams, PharmD, FCCP, BCOP
can result in dose reductions, reductions in dose intensity, Associate Professor
delays in therapy, and discontinuation of therapy. These University of Kentucky College of Pharmacy
types of treatment alterations may ultimately impact the Lexington, Kentucky
clinical outcomes of patients.5 Additionally, CID can com-
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plicate existing medical problems for the patient with can- he extravasation of chemotherapeutic drugs can be a
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cer and can have lethal consequences. The section of this serious adverse event, depending on the agent and the
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pocket guide on treatment guidelines for CID discusses quantity that has escaped out of the vasculature into
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clinical assessment, management, antidiarrheal agents, and the subcutaneous tissue. The true incidence of extravasation
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future directions in the treatment of this complication. is unknown; however, published literature indicates that 0.01%
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As the number of new cancer cases diagnosed each year to 6% of patients receiving chemotherapy experience this
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exceeds 1.4 million, it is clear that preventive measures and adverse event. Regulating the preparation and administration
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collaboration within the health care community are criti- of chemotherapy minimizes the risk for extravasation.
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cal. Additionally, new technologies, new drugs, and broad Chemotherapeutic agents that cause tissue injury after
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educational opportunities will make cancer prevention and extravasation are typically classified as either irritants or
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treatment more effective. It is the hope of the authors that vesicants. Table 1 (pages 9-82) lists information about
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the information provided in this resource will improve the available parenteral chemotherapeutic agents, including
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handling of cancer therapeutic agents and increase safety the extravasation category. The extravasation of irritants
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for health care workers and their patients. It is also hoped can result in local inflammation, pain, and erythema that is
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that the information will improve the treatment of CINV self-limited and does not lead to skin ulceration. In contrast,
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and CID and thus improve quality of life of patients with the extravasation of vesicants can lead to destruction of
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cancer and their families. the full thickness of the skin, which presents as blistering
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and/or ulceration. The likelihood of a vesicant causing skin
References
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ulceration is highly variable and can be predicted to some
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1. American Cancer Society. Cancer statistics 2008. http://www.cancer.org/
degree by the specific agent, volume extravasated, con-
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docroot/PRO/content/PRO_1_1_Cancer_Statistics_2008_Presentation.asp.
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Accessed September 22, 2008. centration of the drug, and handling of the extravasation.
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2. American Cancer Society. Tobacco control country profiles. http://www.cancer. Dactinomycin, mitomycin-C, anthracyclines (daunorubicin,
t e ro h
org/docroot/PRO/content/PRO_1_1_Tobacco_Control_Country_Profiles.asp? doxorubicin, epirubicin, idarubicin), mechlorethamine, and
d.
Accessed July 22, 2007.
vinca alkyloids (vinblastine, vincristine, vindesine [investi-
3. Cancer prevention & early detection facts & figures 2006. http://www.cancer.
gational], and vinorelbine) have a high vesicant potential,
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org/downloads/STT/CPED2006PWSecured.pdf. Accessed October 5, 2006.
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whereas other vesicants rarely cause skin destruction. Some
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4. National Institute for Occupational Safety and Health. Preventing occupa-
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tional exposure to antineoplastic and other HDs in health care settings. NIOSH vesicants, such as doxorubicin, are absorbed into and kill
Publication No. 2004-165. http://www.cdc.gov/niosh/docs/2004-165. Accessed local cells; the agent is then recycled out of the dead cells
October 5, 2006.
and into surrounding cells, resulting in their death. These
5. Arnold RJG, Gabrail N, Raut M, Kim R, Sung J, Zhou Y. Implications of chemo-
drugs can cause damage that is not self-limited and may
therapy-induced diarrhea on dosing intensity. J Clin Oncol. 2004;22(July 15
suppl):6128. require surgery. The actual incidence, appropriate treat-
ment, and outcome of vesicant extravasation is not well

defined by scientific reports; however, the Oncology Nursing

Society and other groups have developed guidelines that Table 1. Indications, Dosing, Administration,
appear to effectively lower the risk for extravasation, as well Special Instructions, Toxicity, and
as decrease the morbidity associated with extravasation. Extravasation Category (content begins on page 11)
The procedure for managing the extravasation of a vesi-
cant consists of 4 sequential steps: 1) stop the administra-
tion of the cytotoxic agent, 2) disconnect the I.V. line as NOTES TO TABLE
close to the patient as possible (note: do not remove at a Use D5W or NS unless otherwise indicated.
this time), 3) aspirate the residual drug through the line, b Instructions for infusion time may vary at the
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and 4) estimate the amount and dose of extravasated physician’s discretion and according to toxicity.
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c If used in combination, only the dosage of the said
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drug. These sequential steps are followed by 3 more steps
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performed in some order or concurrently: 5) apply cold single agent is provided.
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d Dosage may vary at the physician’s discretion and may
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(or warm) compresses (Table 2, pages 83-84), 6) elevate
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require modification, interruption, or discontinuation
the extremity, and 7) administer the antidote or dispersion
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according to toxicity.
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agent (Table 2).
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e Chemotherapy courses should not be repeated
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until recovery from toxicities of previous course is
adequate.
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f In some instances, labeling does not delineate toxicity
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by grade; in some instances, certain toxicities may not
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be more common than those observed with placebo/
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control.
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g Readers are strongly urged to consult the full
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prescribing information before using any medication
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mentioned in this guide.
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h Categorized as a hazardous drug by the National
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Institute for Occupational Safety and Health.
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The drug information in this review is based on product literature that was
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current as of September 2008: http://www.accessdata.fda.gov/scripts/
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cder/drugsatfda/. Micromedex © 1974-2007. Thomson Healthcare. All rights
reserved. Micromedex Healthcare Series USP DI®. Drug Facts & Comparisons.
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St. Louis, MO: Wolters Kluwer Health; 2006. “Extravasation Category” and
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“Handle as Hazardous Drug” are also based on the References and Suggested
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Readings, respectively.
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Aldesleukin
KEY
Proleukin (Novartis Oncology); 22 million–IU powder for injection
5-FU, 5-fluorouracil DMA, N,N-dimethylacetamide

Indications: Adults with metastatic renal cell carcinoma; adults
5-HT3, serotonin type 3 DVT, deep-venous thrombosis with metastatic melanoma
AE, adverse event ECG, electrocardiogram Mode & Vehicle of Administrationa,b: I.V.: add to 50 mL D5W,
ALK-P, alkaline phosphatase EGFR, epidermal growth factor infuse over 15 minutes. Keep concentration of I.V. solutions
receptor between 30 and 70 mcg/mL (18 million units = 1.1 mg).
ALL, acute lymphoblastic leukemia
ALT, alanine aminotransferase
GI, gastrointestinal Usual Single-Agent Dose Rangec-e: 600,000 IU/kg (0.037 mg/
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kg) every 8 hours for a total of 14 doses. Following 9 days of rest,
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H, histamine
AML, acute myeloblastic leukemia the schedule is repeated for a maximum of 28 doses per course.
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HAMA, human anti-mouse
APL, acute promyelocytic Special Precautions/Instructions: Patients with cardiac,
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antibody
leukemia pulmonary, CNS, hepatic, or significant renal impairment should be
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HBV, hepatitis B virus
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ARDS, acute respiratory distress thoroughly evaluated before beginning treatment with aldesleukin.
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syndrome HTN, hypertension These patients are at higher risk for the serious and sometimes
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fatal reactions that can occur with the use of this drug. Pregnancy
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AST, aspartate aminotransferase IM, intramuscular(ly)
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category C.
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AUC, area under the curve IT, intrathecal(ly)
Toxicitiesf,g:
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bid, twice daily LDH, lactate dehydrogenase
Grade 4 (Life-Threatening) Toxicity (>1%)—Oliguria, anuria,
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BMT, bone marrow transplant LV, left ventricular hypotension, respiratory disorder (ARDS, respiratory failure,
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BSA, body surface area LVEF, left ventricular ejection intubation), diarrhea, bilirubinemia, coma, fever, infection, sep-
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fraction sis, supraventricular tachycardia, CV disorder (fluctuations in
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BUN, blood urea nitrogen
blood pressure), MI, ventricular tachycardia, cardiac arrest,
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MI, myocardial infarction
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CBC, complete blood cell (count)
vomiting, thrombocytopenia, coagulation disorder (intravascu-
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CHF, congestive heart failure NHL, non-Hodgkin’s lymphoma lar coagulopathy), creatinine increase, AST increase, acidosis,
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confusion, stupor, psychosis, dyspnea, apnea, acute kidney failure
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NS, normal saline
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CHOP, cyclophosphamide,
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hydroxydaunomycin, Oncovin, NSCLC, non–small-cell lung cancer Boxed Warning—Therapy should be restricted to patients with
prednisone
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normal cardiac and pulmonary functions as defined by thallium
PI, product information
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CLL, chronic lymphoblastic stress testing and formal pulmonary function testing. Should
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leukemia PVC, polyvinyl chloride be administered in a hospital setting under the supervision of a
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qualified physician experienced in the use of anticancer agents.
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CML, chronic myeloblastic RPLS, reversible posterior
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leukoencephalopathy syndrome Associated with capillary leak syndrome. Associated with impaired
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leukemia
neutrophil function (reduced chemotaxis) and with increased risk
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CNS, central nervous system RTU, ready to use
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for disseminated infection, including sepsis and bacterial endo-
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COPD, chronic obstructive SIADH, syndrome of inappropriate carditis. Withhold in patients with moderate to severe lethargy or
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pulmonary disease secretion of antidiuretic hormone somnolence; continued administration may result in coma.
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CV, cardiovascular SIRS, systemic inflammatory Comments—Lower SQ doses have lower rates of toxicity.
response syndrome
CVA, cerebrovascular accident Extravasation Category: Nonirritant
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SOB, shortness of breath
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CVP, cyclophosphamide,
Handle as Hazardous Drugh: Yes1,2
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vincristine, prednisone SQ, subcutaneous(ly)
CYP, cytochrome P-450 tiw, 3 times weekly
D5W, 5% dextrose in water UTI, urinary tract infection

DEHP, di(2-ethylhexyl)phthalate WBC, white blood cell (count)

Alemtuzumab Arsenic trioxide

Campath (Bayer HealthCare Pharmaceuticals); 30-mg/mL Trisenox (Cephalon Oncology); 10-mg/10-mL ampules
single-use vials
Indications: Induction of remission and consolidation in patients
Indications: As a single agent for B-cell CLL with APL who are refractory to, or have relapsed from, retinoid and
anthracycline-based chemotherapy, and whose APL is character-
Mode & Vehicle of Administrationa,b: I.V. infusion over 2 hours. Do
ized by the presence of the t(15;17) translocation or PML/RAR-a
not administer as I.V. push or bolus.
gene expression
Usual Single-Agent Dose Rangec-e: 3 mg/d until infusion reactions
Mode & Vehicle of Administrationa,b: I.V. over 1-2 hours. Increase
≤ grade 2, then 10 mg/d until infusion reactions ≤ grade 2, then
infusion time to 4 hours if acute vasomotor reactions are observed.
30 mg/d 3 times per week on alternate days.
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Usual Single-Agent Dose Rangec-e: 0.15 mg/kg/d until remission
Special Precautions/Instructions: Premedicate with diphenhydra-
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(maximum = 60 days). If patient achieves remission, administer
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mine 50 mg and acetaminophen 500-1,000 mg 30 minutes before
0.15 mg/kg/d 5 days per week × 5 weeks.
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first infusion and each dose escalation. Administer Pneumocystis
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jiroveci pneumonia prophylaxis with trimethoprim-sulfamethoxazole Special Precautions/Instructions: Monitor patient for signs and
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double strength bid 3 times per week (or equivalent). Administer symptoms of arsenic toxicity. If serious, the injection should be
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herpetic prophylaxis with famciclovir 250 mg bid (or equivalent). immediately discontinued, and chelation therapy should be consid-
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Pregnancy category C. ered. A recommended antidote protocol includes dimercaprol and
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penicillamine. Pregnancy category D.
Toxicitiesf,g:
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Toxicitiesf,g:
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Grade 3 or 4 Toxicity (>1%)—Neutropenia, thrombocytopenia, ane-
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mia, fever, rigors, bronchitis/pneumonitis, sepsis, pneumonia, dysp- Grade 3 or 4 Toxicity—Hypokalemia, hypomagnesemia, hyper-
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nea, fatigue, hypotension, urticaria, asthenia, vomiting, anorexia, glycemia, thrombocytopenia, abdominal pain (lower/upper), bone
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back pain, tachycardia/supraventricular tachycardia, pancytopenia, pain, neutropenia, dyspnea, hypoxia, arthralgia, febrile neutropenia,
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rash/maculopapular rash/erythematous rash, pain/skeletal pain, disseminated intravascular coagulation, fatigue, pyrexia, chest
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pain, weakness, ALT increased, hyperkalemia, paresthesia, sepsis,
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HTN, nausea, abdominal pain, cough, bronchospasm, edema/
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peripheral edema, chest pain, malaise, headache, dizziness, diarrhea, myalgia, limb pain, anemia, hypotension, convulsion, coma, pain
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(nonspecific), drug hypersensitivity, constipation, AST increased,
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stomatitis/ulcerative stomatitis/mucositis, constipation, epistaxis,
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depression, somnolence, herpes simplex, moniliasis, infection (other headache, pruritus, upper respiratory tract infection, bacterial
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viral or unidentified), pruritus, increased sweating. infection (nonspecific), back pain, leukocytosis, renal failure, insom-
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nia, pleural effusion
Boxed Warning—Serious (including fatal) cytopenias, infusion reac-
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tions, and infections have been reported. Single doses >30 mg or Boxed Warning—Some patients experience symptoms similar
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cumulative doses >90 mg per week increase the incidence of pan- to APL differentiation syndrome. Can cause ECG abnormalities,
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cytopenia. Monitor patients during infusion and withhold therapy for including QT interval prolongation and complete atrioventricular
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grade 3 or 4 infusion reactions. Gradual dose escalation is required block; monitor ECG and electrolytes according to PI recommenda-
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at the initiation of therapy and after the interruption of therapy for 7 tions.
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or more days. Administer prophylaxis against P. jiroveci pneumonia Extravasation Category: No data
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and herpesvirus infections.
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Handle as Hazardous Drugh: Yes1-5
Extravasation Category: No data
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Asparaginase–Escherichia coli strain Bevacizumab

Elspar (Ovation Pharmaceuticals); injectable 10,000 IU/vial Avastin (Genentech BioOncology); 100-mg/4-mL,
400-mg/16-mL single-use vials
Indications: As part of combination therapy for ALL
Mode & Vehicle of Administrationa,b: IM; I.V. infusion; I.V. slow push Indications: First- or second-line treatment of metastatic carci-
over 30 minutes through side arm of running I.V. noma of the colon or rectum, in combination with I.V. 5-FU–based
chemotherapy; first-line treatment of unresectable, locally
Usual Single-Agent Dose Rangec-e: 6,000 IU/m2 I.V. or IM 3 times advanced, recurrent, or metastatic nonsquamous NSCLC, in
per week. combination with carboplatin and paclitaxel.
Special Precautions/Instructions: Skin test with 2 IU asparaginase Mode & Vehicle of Administrationa,b: The dose should be diluted
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at least 1 hour before dose. Anaphylaxis and serious allergic reac- in NS in a total volume of 100 mL to be administered as an I.V.
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tions, thrombotic events, pancreatitis, glucose intolerance, and
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infusion. The initial dose should be infused over 90 minutes follow-
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coagulopathy can occur. Pregnancy category C. ing chemotherapy. If the first infusion is well tolerated, the second
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Toxicitiesf,g: infusion may be administered over 60 minutes. If the 60-minute
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infusion is well tolerated, all subsequent infusions may be adminis-
All Grades of Toxicity—Allergic reactions (skin rashes, urticaria,
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tered over 30 minutes. Do not administer as I.V. push or bolus.
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arthralgia, respiratory distress, acute anaphylaxis), fatal hyper-
e
Usual Single-Agent Dose Rangec-e: Metastatic carcinoma of the
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thermia, pancreatitis, hyperglycemia, glucosuria, polyuria, hypofi-
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brinogenemia, depression of clotting factors (V, VII, VIII, and IX), colon or rectum: 5 mg/kg or 10 mg/kg every 14 days in combination
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decrease in circulating platelets, consumption coagulopathy, intra- with I.V. 5-FU–based chemotherapy; 5 mg/kg when used in combi-
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cranial hemorrhage and fatal bleeding associated with low fibrino- nation with bolus IFL (irinotecan, 5-FU, leucovorin); 10 mg/kg when
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gen level, fibrinolytic activity increased, depression, somnolence, used in combination with FOLFOX4 (oxaliplatin, 5-FU, leucovorin).
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fatigue, coma, confusion, agitation, hallucinations, Parkinson-like Nonsquamous NSCLC: 15 mg/kg every 3 weeks, in combination
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syndrome, blood ammonia increased, chills, fever, nausea, vomit- with carboplatin and paclitaxel.
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ing, anorexia, abdominal cramps, weight loss, headache, irritabil-
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Special Precautions/Instructions: Bevacizumab should not be
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ity, azotemia, hypoalbuminemia, acute renal shutdown, fatal renal
initiated for at least 28 days following major surgery. The time
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insufficiency, proteinuria, variety of liver abnormalities (elevations
between the last dose of bevacizumab and elective surgery is
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of AST, ALT, ALK-P, bilirubin, depression of serum albumin, cho-
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lesterol, and plasma fibrinogen), lipids increased, lipids decreased, unclear; however, the 20-day half-life of bevacizumab should be
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peripheral edema, fatty changes in liver, malabsorption syndrome, considered when making the decision. Non-GI fistula formation,
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transient bone marrow depression, leukopenia hemorrhage/bleeding, arterial thrombotic events, HTN, RPLS,
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neutropenia, infection, proteinuria, nephrotic syndrome, CHF, and
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No Boxed Warning infusion reactions have been reported in patients receiving beva-
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Extravasation Category: Nonirritant cizumab. If any of these toxicities occur, increased monitoring and
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temporary or permanent discontinuation of bevacizumab may
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Handle as Hazardous Drugh: Yes1-5 be indicated; see PI for details. Blood pressure monitoring should
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be conducted every 2 to 3 weeks during treatment. Patients who
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develop HTN on bevacizumab may require blood pressure monitor-
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ing at more frequent intervals. Patients with bevacizumab-induced
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or -exacerbated HTN who discontinue bevacizumab should con-
tinue to have their blood pressure monitored at regular intervals.
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Patients receiving bevacizumab should be monitored for the devel-
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opment or worsening of proteinuria with serial urinalyses. Patients
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with a ≥2+ urine dipstick reading should undergo further assess-
ment (eg, a 24-hour urine collection). Pregnancy category C.
Toxicitiesf,g:
Grade 3-5 Toxicity (≥2% more frequent vs control)—Asthe-
nia,* abdominal pain, pain,* HTN, DVT,* intra-abdominal thrombo-
sis,* syncope, diarrhea, constipation,* leukopenia,* neutropenia,

nausea, vomiting, dehydration, ileus, neuropathy (sensory), neuro-

logic (other), fatigue, headache, hemorrhage, venous thrombus/ Bleomycin
embolism, infection without neutropenia, infection with grade 3 or Blenoxane (Bristol-Myers Squibb), Teva Pharmaceuticals,
4 neutropenia, febrile neutropenia, pneumonitis/pulmonary infil- various; injectable 15, 30 units/vial
trates, hyponatremia, proteinuria
Boxed Warning—Bevacizumab administration can result in the Indications: Palliative treatment for squamous cell carcinoma of
development of GI perforation, in some instances fatal. GI perfora- the head and neck, penis, cervix, and vulva; testicular carcinoma;
tion should be included in the differential diagnosis of patients pre- Hodgkin’s disease; NHL; malignant pleural effusions
senting with abdominal pain on bevacizumab. Permanently discon-
tinue bevacizumab in patients with GI perforation. Bevacizumab Mode & Vehicle of Administrationa,b: IM; SQ; I.V. infusion in up to
administration can result in the development of wound dehiscence, 50 mL; I.V. push over 10 minutes; intrapleural injection.
A
in some instances fatal. Permanently discontinue bevacizumab in Usual Single-Agent Dose Rangec-e: 10-20 units/m2 IM, SQ, I.V.
ll
patients with wound dehiscence requiring medical intervention. once or twice a week.
ri
gh
Co es
Fatal pulmonary hemorrhage can occur in NSCLC patients treated
Hodgkin’s disease: 1 unit/d or 5 units/wk I.V. or IM maintenance.
ts
py erv
with chemotherapy and bevacizumab. Patients with recent hemop-
ri
tysis should not receive bevacizumab. Sclerosing dose: 60 units in 50-100 mL NS.
gh d.
t
Extravasation Category: No data Special Precautions/Instructions: Skin test or give test dose of
© ep
e
2 units bleomycin before therapeutic dose. Keep total dose to
2 0 ro
Handle as Hazardous Drugh: No data <400 units for single-agent use. In lymphoma patients, give test
08 du
* Reported as grade 3 or 4 only; others reported as grade 3-5. dose of 2 units for the first 2 doses. Cumulative doses ≥400 units
M tio
of bleomycin should be given with great caution. Pregnancy
cM n
category D.
ah in
c
on w
Toxicitiesf,g:
Pu ol
All Grades of Toxicity (≥5%)—Pneumonitis progressing to
bl e o
pulmonary fibrosis, dyspnea, fine rales, idiosyncratic reactions
is
h
hi
(hypotension, mental confusion, fever, chills, and wheezing), ery-
ng n p
thema, rash, striae, vesiculation, hyperpigmentation, skin tender-
G art
ness, hyperkeratosis, nail changes, alopecia, pruritus, stomatitis,
ro
scleroderma-like skin changes, local pain with intrapleural admin-
up wit
istration, vascular toxicities, MI, CVA, thrombotic microangio-
un ho
pathy (hemolytic-uremic syndrome), cerebral arteritis, Raynaud’s
le ut
phenomenon, fever, chills, vomiting, anorexia, weight loss, pain at
ss
tumor site, phlebitis, local reactions, malaise
ot rm
he
Boxed Warning—Pulmonary fibrosis is the most severe toxicity
pe
rw sio
associated with bleomycin; severe idiosyncratic reactions have
is
is
e
been reported.
no s p
Extravasation Category: Nonirritant
t e ro h
i
d.
ib
tei
d.

Bortezomib Busulfan injection

Velcade (Millenium Pharmaceuticals); injectable 3.5 mg/vial Busulfex (PDL BioPharma); 60-mg/10-mL ampules
Indications: Multiple myeloma and mantle cell lymphoma in Indications: In combination with cyclophosphamide as conditioning
patients who have received at least 1 prior therapy regimen prior to allogeneic hematopoietic progenitor cell trans-
Mode & Vehicle of Administrationa,b: 3- to 5-second bolus I.V. plantation for CML
injection. Mode & Vehicle of Administrationa,b: I.V.: mix in D5W or NS to a
Usual Single-Agent Dose Rangec-e: 1.3 mg/m2/dose administered final concentration 0.5 mg/mL. Doses to be infused over 2 hours.
twice weekly for 2 weeks (days 1, 4, 8, and 11) followed by 10-day Usual Single-Agent Dose Rangec-e: 0.8 mg/kg/dose × 16 doses
rest period (days 12-21). prior to cyclophosphamide.
A
ll
For patients with multiple myeloma, may use maintenance sched- Special Precautions/Instructions: Must be infused via a central line.
ri
gh
Co es
ule of once weekly for 4 weeks (days 1, 8, 15, and 22) followed Flush the line with 5 mL NS or D5W before and after each dose.
ts
py erv
by 13 days of rest. At least 72 hours must have elapsed between Pregnancy category D.
ri
doses.
gh d.
Toxicitiesf,g:
t
Special Precautions/Instructions: Caution should be used for
© ep
All Grades of Toxicity (≥20%, through BMT day +28)—Myelosup-
e
patients with neuropathy, history of syncope, hypotension, or liver
2 0 ro
pression (granulocytopenia, thrombocytopenia, anemia), fever,
R
dysfunction. Patients should be counseled to be cautious when using
08 du
headache, asthenia, chills, pain (nonspecific), edema general, allergic
machinery or driving because of potential hypotension, syncope,
M tio
reaction, chest pain, injection site inflammation, back pain, tachycar-
cM n
dizziness, fatigue, and altered vision. Pregnancy category D. dia, HTN, thrombosis, vasodilation, nausea, stomatitis (mucositis),
ah in
c
Toxicitiesf,g: vomiting, anorexia, diarrhea, abdominal pain, dyspepsia, constipa-
on w
Grade 3 or 4 Toxicity (>1%)—Asthenic conditions, nausea, diarrhea, tion, dry mouth, rectal disorder, abdominal enlargement, hypomag-
Pu ol
decreased appetite, constipation, thrombocytopenia, peripheral nesemia, hyperglycemia, hypokalemia, hypocalcemia, hyperbiliru-
bl e o
neuropathy, pyrexia, vomiting, anemia, headache, insomnia, arthral- binemia, edema, ALT elevation, creatinine increased, insomnia, anxi-
is
h
hi
gia, pain in limb, edema, neutropenia, paresthesia and dysesthesia, ety, dizziness, depression, rhinitis, lung disorder, cough, epistaxis,
ng n p
dyspnea, dizziness (excluding vertigo), dehydration, bone pain, dyspnea, rash, pruritus
G art
myalgia, back pain, abdominal pain, hypotension, pneumonia Boxed Warning—Causes profound myelosuppression.
ro
up wit
No Boxed Warning Comments—The solvent used in the formulation, DMA, was studied
un ho
Comments—Toxicities above grade 3 or 4 occurred in ≤30% of in 1962 as a potential cancer chemotherapy drug. Toxicities asso-
le ut
patients; thrombocytopenia, the most common grade 3 or 4 tox- ciated with DMA were hepatotoxicity (liver transaminase levels
ss
icity (approximately 35% incidence), was maximal on day 11, and increased) and neurologic symptoms (hallucinations, somnolence,
ot rm
lethargy, confusion). Daily recommended dose of busulfan injection
he
recovery was seen by the next cycle.
pe
contains DMA equivalent to 42% of the maximal tolerated dose on
rw sio
Extravasation Category: No data a mg/m2 basis. The relative contribution of DMA and/or other con-
is
is
e
Handle as Hazardous Drugh: No data comitant medications to neurologic and hepatic toxicities observed
no s p
with busulfan injection is difficult to ascertain.
t e ro h
i
d.
Extravasation Category: Irritant
ib
tei
d.

Carboplatin Carmustine for injection (BCNU)

Paraplatin (Bristol-Myers Squibb), Teva Pharmaceuticals, BiCNU (Bristol-Myers Squibb Oncology); injectable 100-mg
various; injectable 50-, 150-, 450-, 600-mg vials vials; 3-mL diluent
Indications: Advanced ovarian carcinoma; palliative treatment of Indications: Hodgkin’s disease and NHL (second-line treatment, in
recurrent ovarian carcinoma combination); multiple myeloma (in combination with prednisone);
Mode & Vehicle of Administrationa,b: I.V. infusion over 15 minutes brain tumors (glioblastoma, brain stem glioma, medulloblastoma,
or longer. astrocytoma, ependymoma, and metastatic brain tumors)
Usual Single-Agent Dose Rangec-e: 360 mg/m2 over 15 minutes Mode & Vehicle of Administrationa,b: Slow I.V. infusion in 250-mL
or longer, every 4 weeks. Dosage reductions are recommended for solution over 1-2 hours.
A
ll
renal impairment, or calculate total dose using Calvert formula and Usual Single-Agent Dose Rangec-e: 150-200 mg/m2 every 6
ri
gh
target AUC. weeks. Given as a single dose or divided into 2 daily doses given on
Co es
ts
py erv
Special Precautions/Instructions: Aluminum-containing I.V. consecutive days.
ri
infusion sets and needles should not be used. Renal effects of Special Precautions/Instructions: Avoid contact with skin; may
gh d.
nephrotoxic compounds may be potentiated by carboplatin. cause brown stain; intense pain and burning at injection site if
t
© ep
e
Pregnancy category D. infused too quickly. Rapid infusion causes flushing. Discard if drug
2 0 ro
is an oily film in vial. The safety and effectiveness of carmustine in
R
Toxicitiesf,g:
08 du
pediatric patients have not been established. Pregnancy category D.
M tio
All Grades of Toxicity—Thrombocytopenia; neutropenia; leuko-
Toxicitiesf,g:
cM n
penia; anemia; infections; bleeding; transfusions; nausea/vomiting;
ah in
c
other GI side effects; peripheral neuropathies; ototoxicity; other All Grades of Toxicity—Pulmonary infiltrates and/or fibrosis;
on w
sensory side effects; central neurotoxicity; elevations in serum delayed-onset pulmonary fibrosis; pulmonary hypoplasia; delayed
Pu ol
creatinine, blood urea, bilirubin, AST, ALK-P; electrolyte loss myelosuppression; thrombocytopenia; leukopenia; acute leuke-
bl e o
(sodium, potassium, calcium, magnesium); other (pain, asthenia, mia; bone marrow dysplasias; anemia; nausea/vomiting; increased
is
h
hi
CV, respiratory, allergic, genitourinary, alopecia, mucositis) transaminase, ALK-P, and bilirubin levels; progressive azotemia;
ng n p
Boxed Warning—Bone marrow suppression is dose-related and decreased kidney size; renal failure; kidney damage; flushing;
G art
may be severe, resulting in infection and/or bleeding; anemia may burning at injection site; neuroretinitis; chest pain; headache;
ro
allergic reactions; hypotension; tachycardia
up wit
be cumulative and may require transfusion support; vomiting is
a frequent drug-related side effect; anaphylaxis-like reactions Boxed Warning—Can cause bone marrow suppression, nota-
un ho
have been reported and may occur within minutes of administra- bly thrombocytopenia and leukopenia, which may contribute to
le ut
ss
tion. Epinephrine, corticosteroids, and antihistamines have been bleeding and overwhelming infections in already compromised
ot rm
employed to alleviate symptoms. patients; blood cell counts should be monitored weekly for at
he
least 6 weeks after a dose; dose-related pulmonary toxicity may
pe
rw sio
occur; delayed pulmonary toxicity can occur years after treatment
is
Handle as Hazardous Drugh: Yes1-5 and can result in death.
is
e
no s p
t e ro h
i
d.
ib
tei
d.

artery disease, CHF, or arrhythmias. Close monitoring of serum

Cetuximab electrolytes during and after therapy is recommended.
Erbitux (Bristol-Myers Squibb/ImClone Systems); Extravasation Category: No data
100-mg/50-mL, 200-mg/100-mL single-use vials
Handle as Hazardous Drugh: No data
Indications: In combination with irinotecan for EGFR-expressing, * Rate in head and neck cancer patients is increased by more than
metastatic colorectal carcinoma in patients who are refractory 1% versus radiation alone.
to irinotecan-based chemotherapy; as a single agent for EGFR-
expressing, metastatic colorectal carcinoma in patients who are
intolerant to irinotecan-based chemotherapy; in combination with
radiation therapy for locally or regionally advanced squamous cell
A
carcinoma of the head and neck; as a single agent for recurrent or
ll
metastatic squamous cell carcinoma of the head and neck after
ri
gh
Co es
failure of platinum-based therapy
ts
py erv
Mode & Vehicle of Administrationa,b: Must be administered
ri
gh d.
through a low–protein-binding 0.22-μm in-line filter. Administer
t
as an I.V. infusion over 120 minutes (maximum infusion rate, 5 mL/
© ep
e
min); weekly maintenance dose: I.V. infusion over 60 minutes
2 0 ro
R
08 du
(maximum infusion rate, 5 mL/min).
M tio
Usual Single-Agent Dose Rangec-e: 400-mg/m2 loading dose
cM n
followed by 250-mg/m2 weekly maintenance dose.
ah in
c
on w
Special Precautions/Instructions: Premedication with an anti-
Pu ol
histamine (diphenhydramine 50 mg I.V.) recommended. Do not
bl e o
administer as I.V. push or bolus. Patients should be advised to wear
is
h
hi
sunscreen and hats and limit sun exposure as sunlight can exac-
ng n p
erbate any skin reactions that may occur with cetuximab therapy.
G art
For patients who experience mild to moderate infusion-related
ro
reactions, the infusion rate should be permanently reduced by 50%.
up wit
Pregnancy category C.
un ho
le ut
Toxicitiesf,g:
ss
ot rm
Grade 3 or 4 Toxicity (>1% in colorectal trials and/or >1% vs
he
placebo in head and neck trials)—Cardiopulmonary arrest,*
pe
rw sio
infusion reaction, acneiform rash, radiation dermatitis,* asthenia/
is
malaise, pain, abdominal pain, back pain, headache, mucositis/
is
e
no s p
stomatitis,* xerostomia,* weight loss,* anorexia, dehydration,
t e ro h
nausea, vomiting, constipation, diarrhea, dyspnea, anemia
d.
Boxed Warning—Administration resulted in severe infusion
reactions in approximately 3% of patients, rarely with fatal out-
ib
come (<1 in 1,000). Approximately 90% of these reactions were
tei
associated with the first infusion. Severe infusion reactions require
d.
immediate interruption of cetuximab infusion and permanent dis-
continuation of further treatment. Cardiopulmonary arrest and/
or sudden death occurred in 2% of patients with squamous cell
carcinoma of the head and neck treated with radiation therapy and
cetuximab in comparison with none of the patients receiving radia-
tion alone. Cetuximab in combination with radiation should be used
with caution in head and neck cancer patients with known coronary

ototoxicity, which is more pronounced in children and is manifested

Cisplatin by tinnitus and/or loss of high-frequency hearing and occasionally
Platinol-AQ (Bristol-Myers Squibb), Teva Pharmaceuticals, deafness, is severe. Anaphylaxis-like reactions have been reported.
various; injectable 50-mg/50-mL, 100-mg/100-mL RTU vials Exercise caution to prevent overdose due to confusion with carbo-
platin, and avoid confusion over prescribing practices that fail to dif-
Indications: In combination for metastatic testicular or ferentiate daily doses from total dose per cycle.
ovarian tumors after surgery and/or radiotherapy; second-line
Extravasation Category: Vesicant
monotherapy for refractory metastatic ovarian tumors;
transitional cell bladder cancer that is no longer responsive to Handle as Hazardous Drugh: Yes1-5
local treatments
Mode & Vehicle of Administrationa,b: Aqueous solution should be
A
used I.V. only and administered by I.V. infusion over a 6- to 8-hour
ll
ri
period.
gh
Co es
ts
py erv
Usual Single-Agent Dose Rangec-e: Metastatic testicular tumors:
ri
20 mg/m2 daily × 5 days per cycle (in combination).
gh d.
t
Metastatic ovarian tumors: 100 mg/m2 per cycle, once every
© ep
e
4 weeks (monotherapy) or 75-100 mg/m2 per cycle, once every
2 0 ro
R
08 du
4 weeks (in combination with cyclophosphamide).
M tio
Advanced bladder cancer: 50-70 mg/m2 per cycle, once every
cM n
3-4 weeks.
ah in
c
on w
Special Precautions/Instructions: Aluminum-containing I.V.
Pu ol
infusion sets and needles should not be used. Ensure adequate
bl e o
hydration to prevent drug from binding to renal tubular proteins.
is
h
hi
Hold or reduce dose if serum creatinine is 1.5 mg/dL or higher.
ng n p
Pregnancy category D.
G art
i
Toxicitiesf,g:
ro
up wit
All Grades of Toxicity—Elevations in BUN, creatinine, and serum
un ho
uric acid; decrease in creatinine clearance; renal tubular damage,
le ut
ss
tinnitus, hearing loss, deafness, vestibular toxicity, myelosuppres-
ot rm
sion, leukopenia, thrombocytopenia, anemia, neutropenia, fever,
he
infection, Coombs’-positive hemolytic anemia, acute leukemia,
pe
rw sio
nausea, vomiting, diarrhea, vascular toxicity (MI, CVA, thrombotic
is
microangiopathy, cerebral arteritis), Raynaud’s phenomenon,
is
e
no s p
serum electrolyte disturbances (hypomagnesemia, hypocalcemia,
t e ro h
hyponatremia, hypokalemia, hypophosphatemia), tetany, SIADH,
d.
hyperuricemia, neurotoxicity, peripheral neuropathies, Lhermitte’s
sign, dorsal column myelopathy, autonomic neuropathy, loss
of taste, seizures, muscle cramps, ocular toxicity, optic neuritis,
ib
i
papilledema, cerebral blindness, blurred vision, altered color per-
te
d.
ception, loss of color discrimination, irregular pigmentation of
the retinal macular area, anaphylaxis-like reactions (facial edema,
wheezing, tachycardia, hypotension), hepatotoxicity, transient ele-
vations of liver enzymes, cardiac abnormalities, hiccups, elevated
serum amylase, rash, alopecia, malaise, asthenia
Boxed Warning—Cumulative renal toxicity is severe; other major
dose-related toxicities are myelosuppression, nausea, and vomiting;

Cladribine Clofarabine
Various; injectable preservative-free 10-mg/10-mL vials Clolar (Genzyme Oncology); single-use 20-mg/20-mL vials
Indications: Hairy cell leukemia Indications: Treatment of pediatric patients aged 1 to 21 years with
Mode & Vehicle of Administrationa,b: Dilute in 100-500 mL NS for relapsed or refractory ALL after at least 2 prior regimens
24-hour continuous I.V. infusion. Mode & Vehicle of Administrationa,b: I.V. infusion over 2 hours.
Usual Single-Agent Dose Rangec-e: 0.09 mg/kg/d for 7 days I.V. as Usual Single-Agent Dose Rangec-e: 52 mg/m2/d for 5 consecutive
continuous infusion. days; treatment cycle repeated following recovery or return to
Special Precautions/Instructions: Pregnancy category D. baseline organ function approximately every 2-6 weeks.
A
Toxicitiesf,g: Special Precautions/Instructions: Patients should be monitored
ll
for tumor lysis syndrome and cytokine release syndrome, which
ri
gh
Co es
All Grades of Toxicity—Fever, fatigue, chills, asthenia, diaphoresis, could lead to SIRS/capillary leak syndrome. Treatment should be
ts
py erv
malaise, trunk pain, nausea, decreased appetite, vomiting, diarrhea, stopped immediately if SIRS or capillary leak syndrome develops.
ri
constipation, abdominal pain, purpura, petechiae, epistaxis, neutro- Avoid nephrotoxic and hepatotoxic drugs, which may alter drug
gh d.
penia, anemia, prolonged bone marrow hypocellularity, aplastic clearance and increase drug toxicity, respectively. Pregnancy cat-
t
© ep
anemia, hemolytic anemia, thrombocytopenia, prolonged depres-
e
egory D.
2 0 ro
sion of CD4 counts, pancytopenia, headache, dizziness, insomnia,
R
Toxicitiesf,g:
08 du
neurologic toxicity, edema, tachycardia, abnormal breath sounds,
M tio
cough, abnormal chest sounds, SOB, pulmonary interstitial infil- Incidence More Frequent (≥2% Grade 3 or 4 Toxicity)—Febrile
cM n
trates, injection site reactions, pruritus, pain, erythema, urticaria, neutropenia, neutropenia, transfusion reaction, tachycardia,
ah in
c
rash, hypereosinophilia, myalgia, arthralgia, increases in bilirubin abdominal pain, diarrhea, gingival bleeding, nausea/vomiting,
on w
and transaminases edema, fatigue, mucosal inflammation, pain (nonspecific), pyrexia,
Pu ol
Boxed Warning—Suppression of bone marrow function should be rigors, hepatomegaly, jaundice, infections (bacteremia, cellulitis,
bl e o
anticipated; serious neurologic toxicity (including irreversible para- herpes simplex, oral candidiasis, pneumonia, sepsis, staphylococcal
is
h
hi
paresis and quadriparesis) has been reported; acute nephrotoxicity infection), anorexia, arthralgia, back pain, pain in limb, headache,
ng n p
has been observed with high doses. anxiety, hematuria, dyspnea, epistaxis, pleural effusion, respiratory
G art
distress, dermatitis, palmar–plantar erythrodysesthesia syndrome,
ro
Comments—Most nonhematologic toxicities were mild to moderate petechiae, HTN, hypotension
up wit
in severity.
No Boxed Warning
un ho
Extravasation Category: Nonvesicant
le ut
ss
ot rm
he
pe
rw sio
is
is
e
no s p
n
t e ro h
i
d. ib
tei
d.

Cyclophosphamide Cytarabine
Various; injectable 100-, 200-, 500-mg and 1-, 2-g vials; Various; 100-mg, 500-mg, 1-g, 2-g multiple-dose vials
25-, 50-mg tablets
Indications: In combination with other approved anticancer drugs
Indications: Carcinoma of the breast; adenocarcinoma of the for remission induction in acute nonlymphocytic leukemia in adults
ovaries; acute monocytic leukemia; AML; ALL in children; CLL; and children; useful in treatment of ALL and chronic myelocytic
chronic granulocytic leukemia; Hodgkin’s disease; multiple myelo- leukemia (in blast phase); IT administration indicated for prophy-
ma; mycosis fungoides; neuroblastoma; retinoblastoma laxis and treatment of meningeal leukemia
Mode & Vehicle of Administrationa,b: PO; I.V. infusion. Mode & Vehicle of Administrationa,b: IT; SQ; I.V. push; I.V. infusion.
Usual Single-Agent Dose Rangec-e: I.V. (AML induction): 100-mg/
A
Usual Single-Agent Dose Rangec-e: Up to 40-50 mg/kg I.V.
ll
in divided doses over 2-5 days. Other I.V. regimens include m2 continuous infusion or 100 mg/m2 every 12 hours, days 1-7.
ri
gh
Co es
10-15 mg/kg every 7-10 days or 3-5 mg/kg twice weekly. Oral Special Precautions/Instructions: Use preservative-free solution
ts
py erv
dose is 1-5 mg/kg/d. when reconstituting for high-dose or IT therapy and use immedi-
ri
ately. Pregnancy category D.
gh d.
Special Precautions/Instructions: Administer fluids of at least
t
3 L/d and administer drug early in day, as ambulation helps pre- Toxicitiesf,g:
© ep
e
vent accumulation of drug in bladder. Can cause fetal harm when
2 0 ro
All Grades of Toxicity—Anemia, leukopenia, thrombocytopenia,
R
administered during pregnancy. Forced fluid intake helps prevent
08 du
megaloblastosis, reduced reticulocytes, infection, myalgia, bone
hemorrhagic cystitis. May need to reduce dose or discontinue in
M tio
pain, maculopapular rash, malaise, anorexia, nausea, vomiting,
cM n
patients who develop viral, bacterial, fungal, protozoal, or helmin- diarrhea, oral and anal inflammation/ulceration, hepatic dysfunc-
ah in
thic infections. Pregnancy category D.
c
tion, fever, thrombophlebitis, bleeding, sepsis, pneumonia, cel-
on w
Toxicitiesf,g: lulitis at injection site, skin ulceration, urinary retention, renal
Pu ol
All Grades of Toxicity—Impairment of fertility, nausea, vomit- dysfunction, neuritis, neural toxicity, sore throat, esophageal
bl e o
ing, anorexia, abdominal discomfort, pain, diarrhea, hemorrhagic ulceration, esophagitis, chest pain, pericarditis, bowel necrosis,
is
h
hi
colitis, oral mucosal ulceration, jaundice, alopecia, skin rash, abdominal pain, pancreatitis, freckling, jaundice, conjunctivitis,
ng n p
pigmentation of the skin, changes in nails, Stevens-Johnson dizziness, alopecia, anaphylaxis, allergic edema, pruritus, SOB,
G art
syndrome, toxic epidermal necrolysis, leukopenia, neutropenia, urticaria, headache
ro
up wit
thrombocytopenia, anemia, hemorrhagic cystitis, urinary bladder Boxed Warning—Main toxic effect is bone marrow suppression
fibrosis, hemorrhagic ureteritis, renal tubular necrosis, interstitial with leukopenia, thrombocytopenia, and anemia; less serious toxic-
un ho
pneumonitis, interstitial pulmonary fibrosis, infections, second- ity includes nausea, vomiting, diarrhea, abdominal pain, oral ulcer-
le ut
ss
ary malignancies, anaphylactic reactions, death, SIADH, malaise, ation, hepatic dysfunction.
ot rm
asthenia Comments—Severe and at times fatal CNS, GI, and pulmonary tox-
he
pe
No Boxed Warning icity has been reported following some experimental dose sched-
rw sio
ules.
is
is
e
no s p
t e ro h
d. ib
tei
d.

Dacarbazine Dactinomycin
DTIC-Dome (Bayer HealthCare Pharmaceuticals), Teva Cosmegen (Ovation Pharmaceuticals); injectable 0.5-mg vials
Pharmaceuticals, various; injectable 100-, 200-mg vials
Indications: In combination and/or multimodality therapy for
Indications: Hodgkin’s disease (second-line treatment, in Wilms’ tumor, childhood rhabdomyosarcoma, Ewing’s sarcoma,
combination); metastatic malignant melanoma metastatic nonseminomatous testicular cancer; as monotherapy
Mode & Vehicle of Administrationa,b: I.V. infusion. or in combination for gestational trophoblastic neoplasia; com-
ponent of regional perfusion for locally recurrent or locoregional
Usual Single-Agent Dose Rangec-e: Melanoma: 2-4.5 mg/kg/d × solid malignancies
10 days every 4 weeks or 250 mg/m2/d × 5 days every 3 weeks.
Mode & Vehicle of Administrationa,b: I.V. slow push; I.V. rapid
A
Hodgkin’s disease: 150 mg/m2/d × 5 days combined with other
ll
infusion.
ri
effective drugs every 4 weeks; 375 mg/m2 on day 1 in combination
gh
Usual Single-Agent Dose Rangec-e: 15 mcg/kg daily for 5 days
Co es
with other effective drugs repeated every 15 days.
ts
py erv
(in combination).
Special Precautions/Instructions: Pregnancy category C.
ri
gh d.
Testicular cancer: 1,000 mcg/m2/d (in combination).
Toxicitiesf,g:
t
© ep
Trophoblastic neoplasia: 12 mcg/kg days 1-5 (single agent); 500
e
All Grades of Toxicity—Anorexia, nausea, vomiting, diarrhea,
2 0 ro
mcg days 1, 2 (in combination).
R
flu-like syndrome, myalgias, malaise, alopecia, facial flushing,
08 du
facial paresthesia, liver function test abnormalities, renal function Solid malignancies: Dosages and techniques vary; in general,
M tio
test abnormalities, erythematous rash, urticarial rashes, photo- 50 mcg/kg for lower extremity, 35 mcg/kg for upper extremity.
cM n
sensitivity reactions
ah in
c
Special Precautions/Instructions: Contraindicated in patients
on w
Boxed Warning—Most common toxicity is hematopoietic infected with chickenpox or herpes zoster. Drug has a narrow
Pu ol
depression; hepatic necrosis has been reported; carcinogenic and therapeutic index; do not exceed recommended doses. Pregnancy
bl e o
teratogenic effects when used in animals. Therapeutic benefit must category D.
is
h
be carefully weighed against risk for toxicity.
hi
Toxicitiesf,g:
ng n p
All Grades of Toxicity—Malaise, fatigue, lethargy, fever, myalgia,
G art
i
ro
Handle as Hazardous Drugh: Yes1-5 proctitis, hypocalcemia, growth retardation, infection, cheilitis,
up wit
dysphagia, esophagitis, ulcerative stomatitis, pharyngitis, pneumo-
un ho
nitis, anorexia, nausea, vomiting, abdominal pain, diarrhea, GI
le ut
ulceration, liver toxicity (ascites, hepatomegaly, hepatic veno-
ss
occlusive disease, hepatitis, liver function test abnormalities), ane-
ot rm
mia, aplastic anemia, agranulocytosis, leukopenia, thrombocytope-
he
pe
nia, pancytopenia, reticulocytopenia, alopecia, skin eruptions, acne,
rw sio
flare of erythema, increased pigmentation of previously irradiated
is
is
e
skin, severe damage to soft tissue upon extravasation, epidermo-
no s p
lysis, erythema, edema; many abnormalities of renal, hepatic, and
t e ro h
bone marrow function
d.
Boxed Warning—Drug is highly toxic (corrosive, carcinogenic,
mutagenic, teratogenic); severe damage to soft tissues if extrava-
ib
sation occurs during I.V. administration. Avoid exposure during
tei
pregnancy. Handle powder and solution with care.
d.
Comments—Toxic effects (except nausea and vomiting) usually
do not become apparent until 2-4 days after a course of therapy is
stopped and may not peak until 1-2 weeks have elapsed.

Daunorubicin citrate liposome injection Daunorubicin HCl

DaunoXome (Gilead Sciences); 50-mg daunorubicin base per Cerubidine (Bedford Laboratories), Teva Pharmaceuticals,
25-mL vial various; injectable 20-, 50-mg vials
Indications: Advanced HIV-associated Kaposi’s sarcoma Indications: In combination with other approved anticancer drugs
Mode & Vehicle of Administrationa,b: 1 mg of daunorubicin per for acute nonlymphocytic leukemia (myelogenous, monocytic,
1 mL of D5W; administer over 60 minutes by I.V. infusion. erythroid) in adults and ALL in children and adults
Usual Single-Agent Dose Rangec-e: 40 mg/m2 every 2 weeks. Mode & Vehicle of Administrationa,b: I.V. slow push over 2-3 min-
utes into rapidly flowing I.V. line. I.V. rapid infusion in 50 mL over
Special Precautions/Instructions: Reduce dose by 25% for 10-15 minutes; 100 mL over 30-45 minutes.
A
bilirubin 1.2-3 mg/dL. Reduce dose by 50% for bilirubin >3 mg/dL
ll
or serum creatinine >3 mg/dL. Pregnancy category D. Usual Single-Agent Dose Rangec-e: 45 mg/m2/d days 1, 2, 3 of the
ri
gh
first course; days 1, 2 of subsequent courses.
Co es
Toxicitiesf,g:
ts
py erv
Patients >60 years: 30 mg/m2/d with the above schedule.
ri
Severe Toxicity—Fatigue, fever, diarrhea, nausea, dyspnea, head-
gh d.
ache, allergic reactions, abdominal pain, vomiting, depression, Adult ALL: 45 mg/m2/d days 1, 2, 3.
t
cough, anorexia, increased sweating, edema, abnormal vision,
© ep
Pediatric ALL: 25 mg/m2 day 1 every week (4 courses generally
2 0 ro
neuropathy, chest pain, malaise, stomatitis, tenesmus, neutropenia sufficient for remission).
08 du
Boxed Warning—Potential risk for cardiac toxicity and CHF; severe Children <2 years or <0.5 m2 BSA: calculate dose based on weight
M tio
myelosuppression may occur; a triad of back pain, flushing, and (1 mg/kg).
cM n
chest tightness has been reported during first 5 minutes of infusion.
ah in
c
Special Precautions/Instructions: Cumulative dose should not
on w
Extravasation Category: Irritant exceed 550 mg/m2; cumulative dose should not exceed 300 mg/
m2 in children older than 2 years or 10 mg/kg in children younger
Pu ol
than 2 years or with BSA <0.5 m2; cumulative dose should not
bl e o
is
h
exceed 400 mg/m2 in patients with prior radiation therapy
hi
ng n p
to chest/heart. Reduce dose by 25% for bilirubin 1.2-3 mg/dL.
Pregnancy category D.
G art
i
ro
Toxicitiesf,g:
up wit
All Grades of Toxicity—Myelosuppression, CHF, pericarditis–myo-
un ho
le ut
carditis, alopecia, rash, contact dermatitis, urticaria, nausea, vomit-
ss
ing, mucositis, diarrhea, abdominal pain; if extravasation occurs
ot rm
during administration: severe local tissue necrosis, severe cellulitis,
he
thrombophlebitis, painful induration; acute reactions: anaphylactoid
pe
rw sio
reaction, fever, chills, hyperuricemia
is
is
e
Boxed Warning—Must never be given IM or SQ. Severe local tissue
no s p
necrosis if extravasation occurs during administration; myocardial
t e ro h
i
toxicity may occur during therapy or months to years after termi-
d.
nation of therapy; severe myelosuppression occurs when used in
therapeutic doses; may lead to infection or hemorrhage. Dosage
ib
should be reduced in patients with impaired renal or hepatic
tei
function.
d.

Denileukin diftitox Docetaxel

Ontak (Eisai Inc.); 300-mcg/2-mL single-use vials Taxotere (Sanofi-Aventis); concentrate for injection 20-mg
(0.5 mL polysorbate 80) or 80-mg (2.0 mL polysorbate 80)
Indications: Persistent or recurrent cutaneous T-cell lymphoma single-dose vials with accompanying diluent (13% ethanol in
expressing the CD25 component of the interleukin-2 receptor water for injection)
Mode & Vehicle of Administrationa,b: I.V. infusion over at least
15 minutes. The rate may need to be slowed or the infusion discon- Indications: Locally advanced or metastatic breast cancer after
tinued if hypersensitivity reaction occurs. failure of prior chemotherapy; in combination with doxorubicin and
Usual Single-Agent Dose Rangec-e: 9 or 18 mcg/kg/d × 5 days cyclophosphamide for adjuvant treatment of operable node-posi-
every 21 days. tive breast cancer; as a single agent for locally advanced or meta-
A
ll
static NSCLC after failure of prior platinum-based chemotherapy;
Special Precautions/Instructions: Patients with a known hyper-
ri
in combination with cisplatin for unresectable, locally advanced, or
gh
Co es
sensitivity to diphtheria toxin or interleukin-2 should not receive
metastatic chemotherapy-naïve NSCLC; in combination with pred-
ts
py erv
denileukin. Because of the high incidence of acute hypersensitivity
r
nisone for androgen-independent (hormone-refractory) metastatic
ri
reactions, I.V. antihistamines, corticosteroids, and epinephrine as
gh d.
prostate cancer; in combination with cisplatin and 5-FU for treat-
well as resuscitative equipment should be available during denileu-
t
ment-naïve advanced gastric adenocarcinoma, including adeno-
© ep
e
kin administration. Hypersensitivity reactions may occur regardless
carcinoma of the gastroesophageal junction; in combination with
2 0 ro
of treatment cycle. Pregnancy category C.
08 du
cisplatin and 5-FU for locally advanced squamous cell carcinoma of
Toxicitiesf,g: the head and neck
M tio
cM n
Grade 3 or 4 Toxicity (>1%)—Infection, chills/fever, asthenia, Mode & Vehicle of Administrationa,b: I.V. infusion over 1 hour.
ah in
c
transaminase increase, edema, nausea/vomiting, hypoalbu-
Usual Single-Agent Dose Rangec-e: Locally advanced/metastatic
on w
minemia, dyspnea, pain, rash, hypotension, anorexia, dehy-
breast cancer: 60-100 mg/m2 every 3 weeks.
Pu ol
dration, chest pain, anemia, confusion, thrombotic events,
bl e o
weight decrease, headache, arrhythmia, diarrhea, leukopenia, Other indications: 75 mg/m2 every 3 weeks.
is
h
hi
hypocalcemia, insomnia, pruritus, hematuria, thrombocytope- Special Precautions/Instructions: All patients should be pre-
ng n p
nia, myalgia, cough increase, injection site reaction, vasodila- medicated with oral corticosteroids such as dexamethasone 8 mg
G art
tion, tachycardia, constipation, dysphagia, arthralgia, dizziness, bid for 3 days beginning 1 day prior to docetaxel. Pregnancy cat-
ro
paresthesia, nervousness, rhinitis, sweating, albuminuria, pyuria, egory D.
up wit
creatinine increase
Toxicitiesf,g:
un ho
Boxed Warning—Only physicians experienced in the use of anti-
le ut
Grade 3 or 4 or “Severe” AEs—Neutropenia, leukopenia, ane-
ss
neoplastic therapy and management of patients with cancer should
mia, febrile neutropenia, infection, septic death, nonseptic death,
ot rm
use denileukin diftitox. Patients treated with denileukin diftitox
he
must be managed in a facility equipped and staffed for cardiopul- fever in absence of infection, hypersensitivity reaction, fluid reten-
pe
rw sio
monary resuscitation and where the patient can be closely moni- tion, neurosensory changes, neuromotor changes, cutaneous/nail
is
tored for an appropriate period based on his or her health status. changes, diarrhea, stomatitis, asthenia, myalgia, dyspnea
is
e
no s p
Comments—Occurrence of AEs tended to diminish in frequency Boxed Warning—Treatment-related mortality is increased with
t e ro h
after first 2 courses. higher doses, in patients with abnormal liver function, and in NSCLC
d.
patients who have received prior platinum-based chemotherapy
Extravasation Category: No data and who receive single-agent docetaxel 100 mg/m2; neutropenia
Handle as Hazardous Drug#: Yes1,2,4 (which may be severe and result in infections) and severe hyper-
ib
i
sensitivity reactions and fluid retention have occurred; patients
te
d.
with elevated hepatic enzymes and/or ALK-P should generally not
receive docetaxel.

Doxorubicin Doxorubicin HCl liposome injection

Adriamycin PFS (Bedford Laboratories), Teva Doxil (Tibotec Therapeutics, a division of Ortho Biotech);
Pharmaceuticals, various; 10-, 20-, 50-, 150-mg vials as lyo- 20-mg/10-mL, 50-mg/30-mL liposomal dispersion in glass vials
philized powder; 10-, 20-, 50-, 75-, 150-, 200-mg vials as RTU
solution Indications: Ovarian cancer in patients whose disease has
progressed on, or recurred after, platinum-based chemotherapy;
AIDS-related Kaposi’s sarcoma in patients whose disease has
Indications: ALL; AML; Wilms’ tumor; neuroblastoma; soft tissue/
progressed after prior combination chemotherapy or in patients
bone sarcomas; carcinoma of the breast, ovaries, and thyroid; transi-
who are intolerant of such therapy; multiple myeloma in combina-
tional cell bladder carcinoma; gastric carcinoma; Hodgkin’s disease;
tion with bortezomib for patients who have not received bortezo-
malignant lymphoma; bronchogenic carcinoma in which the small
A
mib and have received at least 1 prior therapy
ll
cell histologic type is most responsive compared with other types;
ri
adjuvant therapy in women with evidence of axillary lymph node Mode & Vehicle of Administrationa,b: I.V. infusion at a rate of
gh
Co es
involvement following resection of primary breast cancer 1 mg/min. Rapid infusions may increase infusion-related reactions.
ts
py erv
r
ri
Mode & Vehicle of Administrationa,b: I.V. slow push over 3-5 Usual Single-Agent Dose Rangec-e: Ovarian carcinoma:
gh d.
minutes; I.V. rapid infusion in 50-100 mL NS or D5W over 20-30 50 mg/m2 once every 4 weeks.
t
© ep
e
minutes; continuous infusion for 24-96 hours via pump. AIDS-related Kaposi’s sarcoma: 20 mg/m2 once every 3 weeks.
2 0 ro
Usual Single-Agent Dose Rangec-e: 60-75 mg/m2 every 21 days. Initial rate of 1 mg/min should be used; if no infusion-related AEs
08 du
As part of combination therapy: 40-60 mg/m2 every 21 to 28 days. are observed, the infusion rate should be increased to complete
M tio
the administration over 1 hour.
cM n
Special Precautions/Instructions: Lifetime cumulative dose
ah in
c
should not exceed 550 mg/m2. Cumulative dose in patients who Multiple myeloma: 30 mg/m2 on day 4 following bortezomib
on w
have received radiation therapy to the mediastinal area should not 1.3-mg/m2 I.V. infusion on days 1, 4, 8, 11.
Pu ol
exceed 450 mg/m2. Dose reductions based on serum bilirubin. May Special Precautions/Instructions: Do not administer IM or SQ, as
bl e o
give cardioprotectant dexrazoxane when 300-mg/m2 lifetime dose a bolus injection, or in undiluted solution. Doxorubicin HCl liposome
is
h
is reached. Pregnancy category D.
hi
injection is an irritant; avoid extravasation. Do not use in-line filter
ng n p
f,g or mix with other drugs. May require dose reduction in patients with
Toxicities :
G art
hepatic dysfunction. Liposomal doxorubicin should not be substi-
ro
All Grades of Toxicity—Secondary AML, myelosuppression,
tuted for doxorubicin HCl on a mg/mg basis. Consider pretreatment
up wit
cardiotoxicity (cardiomyopathy, CHF, arrhythmias), alopecia,
with or concomitant use of antiemetics. Pregnancy category D.
un ho
hyperpigmentation of nail beds and dermal crease, onycholysis,
Toxicitiesf,g:
le ut
nausea, vomiting, mucositis (stomatitis/esophagitis), colon ulcer-
ss
ation/necrosis, anorexia, diarrhea, phlebosclerosis, facial flushing, Grade 3 or 4 Toxicity (≥5%)—Neutropenia, anemia, thrombo-
ot rm
cellulitis, fever, chills, urticaria, sensory or motor disturbances, con- cytopenia, palmar-plantar erythrodysesthesia, stomatitis, nausea,
he
pe
junctivitis, lacrimation, tissue necrosis with vesication asthenia, abdominal pain, vomiting, intestinal obstruction, hand–
rw sio
foot syndrome, fever, alopecia, anemia, diarrhea
is
Boxed Warning—Severe local tissue necrosis if extravasation
is
e
occurs during administration; secondary AML or myelodysplas-
no s p
Boxed Warning—Myocardial damage may lead to CHF and may be
tic syndrome has been reported; myocardial toxicity may occur;
t e ro h
encountered as the total cumulative dose approaches 550 mg/m2;
d.
severe myelosuppression may occur; dosage should be reduced in cumulative dosing calculations should include prior anthracycline
patients with impaired hepatic function. and anthracenedione therapy; it should be assumed that doxorubi-
Extravasation Category: Vesicant cin liposome injection will cause myocardial toxicity similar to that
ib
i
of conventional formulations of doxorubicin HCl; acute infusion-
te
d.
associated reactions have occurred in up to 10% of patients; severe
myelosuppression may occur; dosage should be reduced in patients
with impaired hepatic function; accidental substitution of liposomal
doxorubicin for doxorubicin HCl has resulted in severe side effects.

Epirubicin Etoposide
Ellence (Pfizer Oncology), Teva Pharmaceuticals, various; VePesid (Bristol-Myers Squibb), Toposar (Teva
50-mg/25-mL, 200-mg/100-mL vials Pharmaceuticals), various; injectable 100-mg/5-mL, 150-mg/
7.5-mL, 500-mg/25-mL, 1-g/50-mL multiple-dose vials; 50-mg
Indications: Component of adjuvant therapy in patients with capsules
evidence of axillary node tumor involvement following resection of
primary breast cancer Indications: Injection: refractory testicular tumor (in combination)
Mode & Vehicle of Administrationa,b: Administer through a Injection and capsules: small-cell lung cancer (first-line treatment,
free-flowing I.V. over 3-20 minutes. Direct I.V. push is not recom- in combination)
mended. Mode & Vehicle of Administrationa,b: PO; I.V. infusion over at
A
ll
Usual Single-Agent Dose Rangec-e: 100-120 mg/m2 (given either least 30-60 minutes.
ri
gh
Co es
as a single infusion or in 2 divided doses administered on days 1 Usual Single-Agent Dose Rangec-e: Testicular cancer:
ts
py erv
and 8 of the cycle). 50-100 mg/m2/d I.V. × 5 days or 100 mg/m2/d I.V. days 1, 3, 5
ri
Special Precautions/Instructions: Dose modifications required every 3-4 weeks.
gh d.
t
in patients with hepatic dysfunction. Increased risk for CHF with Small-cell lung cancer: 35 mg/m2/d I.V. × 4 days or 50 mg/m2 I.V.
© ep
e
cumulative doses >900 mg/m2. Cimetidine increases epirubicin lev- × 5 days.
2 0 ro
els by 50%, and therefore the 2 drugs should not be used together.
08 du
Patients receiving 120 mg/m2 should receive prophylactic antibiot- Oral: twice the I.V. dose rounded to nearest 50 mg.
M tio
ics because of the chance of severe myelosuppression. Pregnancy Special Precautions/Instructions: Do not give by rapid I.V.
cM n
category D. infusion. Pregnancy category D.
ah in
c
on w
Toxicitiesf,g: Toxicitiesf,g:
Pu ol
Grade 3 or 4 Toxicity (Acute Events)—Neutropenia, leukopenia, All Grades of Toxicity—Myelosuppression, neutropenia, leuko-
bl e o
alopecia, nausea/vomiting, mucositis, febrile neutropenia, anemia, penia, thrombocytopenia, anemia, acute leukemia, nausea, vomit-
is
h
hi
thrombocytopenia, hot flashes, lethargy, infection, diarrhea ing, abdominal pain, anorexia, diarrhea, stomatitis, hepatic, ana-
ng n p
Boxed Warning—Severe local tissue necrosis if extravasation phylaxis-like reactions (chills, fever, tachycardia, bronchospasm,
G art
dyspnea, hypotension), HTN, flushing, facial/tongue swelling,
i
occurs during administration; must not be given IM or SQ; myo-
ro
coughing, diaphoresis, cyanosis, tightness in throat, laryngospasm,
up wit
cardial toxicity may occur; secondary AML has been reported;
severe myelosuppression may occur; dosage should be reduced in back pain, loss of consciousness, apnea, rash, urticaria, pruritus,
un ho
alopecia, aftertaste, fever, pigmentation, abdominal pain, consti-
le ut
patients with impaired hepatic function.
pation, dysphagia, transient cortical blindness, recall dermatitis,
ss
Comments—Delayed toxicities were also observed and included hepatic toxicity, metabolic acidosis, peripheral neurotoxicity,
ot rm
cardiac toxicity (asymptomatic drops in LVEF, CHF) and AML.
he
death, mucositis/esophagitis, asthenia, fatigue, malaise, somno-
pe
rw sio
Extravasation Category: Vesicant lence, optic neuritis, interstitial pneumonia/pulmonary fibrosis,
is
seizure, Stevens-Johnson syndrome, toxic epidermal necrolysis
is
e
no s p
Boxed Warning—Severe myelosuppression with resulting infection
t e ro h
or bleeding may occur.
d.
ib
tei
d.

Floxuridine Fludarabine
Various; for intra-arterial infusion 500-mg vial as a Fludara (Bayer HealthCare Pharmaceuticals), Teva
lyophilized powder Pharmaceuticals, various; injectable 50-mg vial as a lyophilized
solid cake; injectable 25-mg/mL solution
Indications: Palliative management of GI adenocarcinoma meta-
static to the liver Indications: Refractory B-cell CLL
Mode & Vehicle of Administrationa,b: Continuous intra-arterial Mode & Vehicle of Administrationa,b: I.V. infusion in 100 mL D5W
infusion. or NS over 30 minutes.
Usual Single-Agent Dose Rangec-e: 0.1-0.6 mg/kg/d. Usual Single-Agent Dose Rangec-e: 25 mg/m2/d I.V. × 5 days every
A
Special Precautions/Instructions: Use arterial pump for 4 weeks.
ll
ri
administration. Pregnancy category D. Special Precautions/Instructions: Careful attention to correct dose;
gh
Co es
Toxicitiesf,g: severe neurologic effects, including blindness, coma, and death,
ts
py erv
occurred in 36% of patients treated with doses 4 times greater
ri
All Grades of Toxicity—Nausea, vomiting, diarrhea, enteritis,
gh d.
than the recommended dose. Pregnancy category D.
stomatitis, localized erythema, anemia, leukopenia, thrombo-
t
© ep
Toxicitiesf,g:
e
cytopenia; elevations in ALK-P, serum transaminase, serum bili-
2 0 ro
rubin, and LDH; duodenal ulcer, duodenitis, gastritis, bleeding, All Grades of Toxicity—Myelosuppression (neutropenia, thrombo-
08 du
gastroenteritis, glossitis, pharyngitis, anorexia, cramps, abdomi- cytopenia, anemia), fever, chills, fatigue, infection, pain, malaise,
M tio
nal pain, possible intra- and extrahepatic biliary sclerosis, acalcu- diaphoresis, anaphylaxis, hemorrhage, hyperglycemia, dehydration,
cM n
lous cholecystitis, alopecia, dermatitis, nonspecific skin toxicity, weakness, paresthesia, headache, visual disturbance, hearing loss,
ah in
c
rash, myocardial ischemia, fever, lethargy, malaise, weakness, lab sleep disorder, depression, cerebellar syndrome, impaired menta-
on w
abnormalities (sulfobromophthalein sodium, prothrombin, total tion, cough, pneumonia, dyspnea, sinusitis, upper respiratory infec-
Pu ol
protein, sedimentation rates, thrombocytopenia), procedural tion, epistaxis, hemoptysis, bronchitis, hypoxia, nausea/vomiting,
bl e o
complications of regional arterial infusion (arterial aneurysm, diarrhea, anorexia, stomatitis, GI bleeding, esophagitis, mucositis,
is
h
hi
ischemia, thrombosis, embolism, fibromyositis, thrombophlebitis, liver failure, liver function test abnormalities, constipation, dys-
ng n p
hepatic necrosis, abscesses, catheter site infection/bleeding, phagia, rash, pruritus, seborrhea, dysuria, urinary infection, hematu-
G art
catheter blockage, displacement, leakage) ria, renal failure, abnormal renal function, proteinuria, edema, DVT,
ro
up wit
Boxed Warning—Because of the possibility of severe toxic phlebitis, transient ischemic attack, aneurysm, myalgia, osteoporo-
sis, arthralgia, tumor lysis syndrome
un ho
reactions, all patients should be hospitalized for initiation of the
le ut
first course of therapy. Boxed Warning—Can severely suppress bone marrow function;
ss
Comments—Adverse reactions to the arterial infusion of floxuri- associated with severe neurologic effects when used at high
ot rm
doses (4 times greater than the recommended dose) in patients
he
dine are generally related to procedural complications. Other AEs
pe
with acute leukemia, although similar severe CNS toxicity rarely
rw sio
have not been reported with floxuridine but have been noted
reported in patients treated at recommended doses; instances of
is
following administration of 5-FU. Although the possibility of these
is
e
occurring after floxuridine therapy is remote because of its regional life-threatening and sometimes fatal autoimmune hemolytic anemia
no s p
administration, one should be alert for these reactions given the have been reported; in combination with pentostatin for treatment
t e ro h
of refractory CLL, there was an unacceptably high incidence of
d.
pharmacologic similarity between the 2 drugs.
fatal pulmonary toxicity.
ib
Handle as Hazardous Drugh: Yes
tei
d.

5-Fluorouracil (5-FU) Fulvestrant

Adrucil (Teva Pharmaceuticals), various; 50-mg/mL injection; Faslodex (AstraZeneca Pharmaceuticals); 250-mg/5-mL,
1% and 5% topical cream; 0.5%, 2%, 5% topical solution 125-mg/2.5-mL prefilled syringe
Indications: Injection: palliative management of carcinoma of the Indications: Hormone receptor–positive metastatic breast cancer
breast, colon, rectum, stomach, and pancreas in postmenopausal women with disease progression following
Topicals: basal cell carcinoma of the skin (5% strength) and anti-estrogen therapy
multiple actinic (solar) keratoses
Mode & Vehicle of Administrationa,b: IM
Mode & Vehicle of Administrationa,b: I.V. push; topical.
Usual Single-Agent Dose Rangec-e: 250 mg every month slowly
Usual Single-Agent Dose Rangec-e: I.V.: 12 mg/kg daily for 4
A
administered into buttock as either a single 5-mL injection or
ll
days. If no toxicity is observed, 6 mg/kg given on days 6, 8, 10, and 2 concurrent 2.5-mL injections.
ri
gh
12. There is no therapy on days 5, 7, 9, and 11.
Co es
Special Precautions/Instructions: Can cause fetal harm when
ts
py erv
Topical: apply cream or solution twice daily. administered during pregnancy. Should not be administered
ri
gh d.
Special Precautions/Instructions: Leucovorin I.V. given with 5-FU to patients with bleeding diathesis, with thrombocytopenia, or
t
to potentiate effect in some colorectal cancers. Daily 5-FU dose receiving anticoagulants. Pregnancy category D.
© ep
e
should not exceed 800 mg. Pregnancy category D. Toxicitiesf,g:
2 0 ro
R
08 du
Toxicitiesf,g: All Grades of Toxicity (≥5%)—Asthenia, pain, headache,
M tio
All Grades of Toxicity—Stomatitis, esophagopharyngitis, diar- back pain, abdominal pain, injection site pain, pelvic pain,
cM n
rhea, anorexia, nausea, emesis, leukopenia, alopecia, dermatitis, chest pain, flu syndrome, fever, vasodilation, nausea, vomiting,
ah in
c
pruritic maculopapular rash, pancytopenia, thrombocytope- constipation, diarrhea, anorexia, nutritional disorder, peripheral
on w
nia, agranulocytosis, anemia, myocardial ischemia, angina, GI edema, bone pain, dizziness, insomnia, paresthesia, depression,
Pu ol
ulceration/bleeding, anaphylaxis, generalized allergic reactions, anxiety, pharyngitis, dyspnea, cough increased, rash, sweating,
bl e o
acute cerebellar syndrome, nystagmus, headache, dry skin, UTI
is
h
hi
fissuring, photosensitivity, vein pigmentation, palmar–plantar No Boxed Warning
ng n p
erythrodysesthesia syndrome, lacrimal duct stenosis, visual chang-
G art
es, lacrimation, photophobia, disorientation, confusion, euphoria,
ro
Handle as Hazardous Drugh: Yes2
up wit
thrombophlebitis, epistaxis, nail changes
un ho
Boxed Warning—Because of the possibility of severe toxic
le ut
reactions, it is recommended that patients be hospitalized at least
ss
during the initial course of therapy.
ot rm
he
pe
rw sio
is
is
e
no s p
n
t e ro h
i
d. ib
tei
d.

Gemcitabine Gemtuzumab ozogamicin

Gemzar (Eli Lilly and Company); 200-mg and 1-g single-use Mylotarg (Wyeth); injectable 5-mg/20-mL vial as a
vials as a lyophilized powder lyophilized powder
Indications: First-line treatment of metastatic breast cancer (in Indications: Treatment of patients with CD33-positive AML in first
combination with paclitaxel) after failure of prior anthracycline- relapse who are 60 years of age or older and who are not consid-
containing adjuvant chemotherapy (unless anthracyclines were ered candidates for cytotoxic chemotherapy
contraindicated); first-line treatment of inoperable, locally advanced, Mode & Vehicle of Administrationa,b: I.V. in 100 mL NS to infuse
or metastatic NSCLC (in combination with cisplatin); first-line over 2 hours. Must infuse through a low–protein-binding 1.2-μm fil-
treatment of locally advanced or metastatic adenocarcinoma of ter. Infusion bags should be protected from light with an ultraviolet
A
the pancreas after previous treatment with 5-FU; advanced ovarian protective bag. Do not administer as I.V. push or bolus.
ll
cancer (in combination with carboplatin) that has relapsed at least 6
ri
Usual Single-Agent Dose Rangec-e: 9 mg/m2 for 2 doses, with 14
gh
Co es
months after completion of platinum-based therapy
ts
py erv
days between doses.
Mode & Vehicle of Administrationa,b: May give as a concentrated
ri
Special Precautions/Instructions: Gemtuzumab is light-sensitive
gh d.
solution or further dilute in NS and give I.V. over 30 minutes.
and must be protected from direct and indirect sunlight and
t
Usual Single-Agent Dose Rangec-e: Breast cancer (with pacli-
© ep
e
unshielded fluorescent light during preparation and administration.
2 0 ro
taxel): 1,250 mg/m2 on days 1 and 8 of each 21-day cycle. All preparation should take place in a biologic safety hood with the
08 du
NSCLC (with cisplatin): 1,000 mg/m2 on days 1, 8, and 15 of each fluorescent light off. Because of the potential for infusion-related
M tio
28-day cycle or 1,250 mg/m2 on days 1 and 8 of each 21-day cycle. AEs, patients should be premedicated with acetaminophen 650-
cM n
Pancreatic cancer (single agent): 1,000 mg/m2 weekly for up to 1,000 mg PO and diphenhydramine 50 mg PO. Vital signs should
ah in
c
7 weeks, followed by a week of rest. Subsequent cycles should be monitored during infusion and for 4 hours following infusion.
on w
consist of infusions once weekly for 3 consecutive weeks out of Precautions for tumor lysis syndrome should be taken if peripheral
Pu ol
every 4 weeks. WBC >30,000/mcL before administration. Pregnancy category D.
bl e o
Ovarian cancer (with carboplatin): 1,000 mg/m2 on days 1 and 8 of
is
h
Toxicitiesf,g:
hi
each 21-day cycle.
ng n p
Severe or Grade 3 or 4 Toxicity—Sepsis, fever, chills, HTN, nausea,
Special Precautions/Instructions: Infusion times >60 minutes or
G art
dyspnea, hypotension, asthenia, neutropenic fever, pneumonia,
ro
treatments more frequent than weekly dosing have been shown to LDH increased, hypokalemia, abnormal lab values (platelet count,
up wit
increase toxicity. Patients receiving gemcitabine should be moni- absolute neutrophil count, WBC, lymphocytes, hemoglobin, total
un ho
tored before each dose with a CBC, including differential and platelet bilirubin, AST, glucose, calcium, ALT, prothrombin time, ALK-P,
le ut
counts. If marrow suppression is detected, therapy should be modi- partial thromboplastin time, creatinine)
ss
fied or suspended as specified in prescribing information. Pulmonary
ot rm
Boxed Warning—Severe myelosuppression occurs at the recom-
toxicity has been reported; discontinue treatment if severe and insti-
he
mended doses; administration can result in hypersensitivity reac-
pe
tute appropriate supportive care measures. Hemolytic-uremic syn-
rw sio
tions (including anaphylaxis) and other infusion-related reactions,
drome and/or renal failure has been reported. Renal failure leading to
is
which may include pulmonary events; hepatotoxicity has been
is
e
death or requiring dialysis has been rarely reported. The majority of
no s p
reported in association with the use of gemtuzumab ozogamicin,
cases of renal failure leading to death were due to hemolytic-uremic
t e ro h
including severe hepatic veno-occlusive disease.
syndrome. Serious hepatotoxicity, including liver failure and death,
d.
has been reported very rarely. Pregnancy category D. Extravasation Category: No data
Toxicitiesf,g: Handle as Hazardous Drugh: Yes1-4
ib
tei
Grade 3 or 4 Toxicity (>1% single-agent toxicity)—Anemia,
d.
leukopenia, neutropenia, thrombocytopenia; elevated ALT, AST,
ALK-P, bilirubin; nausea/vomiting, pain, constipation, diarrhea,
somnolence
No Boxed Warning

Goserelin Ibritumomab tiuxetan and indium-111 (In-111)/

Zoladex (AstraZeneca Pharmaceuticals); 3.6-preloaded yttrium-90 (Y-90) ibritumomab tiuxetan
syringe: 3-month, 10.8-mg implant Zevalin (Biogen Idec); supplied in 2 separate kits containing all
nonradioactive ingredients
Indications: Palliative treatment of advanced prostate carcinoma;
in combination with flutamide for locally confined stage T2b-T4 Indications: Relapsed or refractory low-grade, follicular, or trans-
(stage B2-C) prostate carcinoma; 3.6-mg formulation also indicated formed B-cell NHL, including rituximab-refractory follicular NHL
in endometriosis, endometrial thinning, and palliative treatment of Mode & Vehicle of Administrationa,b: I.V. injection over 10 minutes.
advanced breast cancer in pre- and perimenopausal women Do not administer IM or SQ.
Mode & Vehicle of Administrationa,b: SQ Usual Single-Agent Dose Rangec-e: Each administration of ibritu-
A
ll
Usual Single-Agent Dose Rangec-e: 3.6 mg every 28 days into the momab tiuxetan should be preceded by a single dose of rituximab.
ri
gh
Co es
upper abdominal wall; 10.8-mg implant given once every 12 weeks. In-111 ibritumomab tiuxetan 5.0 mCi (1.6-mg total antibody dose),
ts
py erv
Special Precautions/Instructions: Temporary increase in tes- followed 7-9 days later (if biodistribution is acceptable) by Y-90
ri
ibritumomab tiuxetan 0.4 mCi/kg (maximum dose, 32 mCi).
gh d.
tosterone levels with first doses may cause increased bone pain
t
and even spinal cord compression in some patients. Pregnancy Special Precautions/Instructions: Ibritumomab tiuxetan doses
© ep
e
category D. must be given within 4 hours of completing a rituximab 250-mg/
2 0 ro
R
m2 dose, which is infused following the guidelines listed under the
08 du
f,g
Toxicities :
“Rituximab” entry in this guide. Biodistribution must be evaluated
M tio
All Grades of Toxicity (>1%)—Hot flashes, vaginitis, headache,
cM n
at 48-72 hours after In-111 ibritumomab tiuxetan. If platelet count is
lability, libido decreased, sweating, depression, acne, breast
low (between 100,000 and 149,000/mm3), decrease dose of Y-90
ah in
c
atrophy, seborrhea, peripheral edema, breast enlargement, pelvic
on w
ibritumomab tiuxetan to 0.3 mCi/kg. Secondary AML and myelo-
symptoms, pain, dyspareunia, libido increased, infection, asthenia, dysplastic syndromes were reported in 5.2% of patients in clinical
Pu ol
nausea, hirsutism, insomnia, breast pain, abdominal pain, back pain, studies and 1.5% of patients in an expanded-access trial. During
bl e o
flu syndrome, dizziness, application site reaction, voice alterations,
is
h
and after radiolabeling with In-111 or Y-90, care should be taken
hi
pharyngitis, hair disorders, myalgia, nervousness, weight gain, leg to minimize radiation exposure to patients and medical personnel.
ng n p
cramps, appetite increased, pruritus, hypertonia Medications for the treatment of hypersensitivity reactions should
G art
i
ro
No Boxed Warning be available for immediate use in the event of an allergic reaction
up wit
Extravasation Category: Nonirritant during administration. Patients who have received murine proteins
un ho
should be screened for human anti-mouse antibodies (HAMA),
Handle as Hazardous Drugh: Yes2,3,5
le ut
as evidence of HAMA may increase the risk for allergic or serious
ss
hypersensitivity reactions. Pregnancy category D.
ot rm
Toxicitiesf,g:
he
pe
rw sio
Grade 3 or 4 Toxicity (>1%)—Thrombocytopenia, neutropenia,
is
anemia, pancytopenia, asthenia, infection, abdominal pain, dyspnea;
is
e
no s p
rituximab, which is part of this therapy, can also cause toxicity as
t e ro h
listed under the “Rituximab” entry in this guide
d.
Boxed Warning—Deaths have occurred within 24 hours of ritux-
imab infusion, an essential component of this therapeutic regimen.
ib
These fatalities were associated with an infusion reaction symptom
tei
complex that included hypoxia, pulmonary infiltrates, ARDS, MI,
d.
ventricular fibrillation, or cardiogenic shock. Approximately 80%
of fatal infusion reactions occurred in association with the first
rituximab infusion. Patients who develop severe infusion reactions
should have rituximab and In-111/Y-90 ibritumomab tiuxetan infu-
sions discontinued and receive medical treatment. Administration
of Y-90 ibritumomab tiuxetan results in severe and prolonged
cytopenias in most patients. This therapeutic regimen should not

be administered to patients with ≥25% lymphoma marrow involve-

ment and/or impaired bone marrow reserve. Severe cutaneous Idarubicin
and mucocutaneous reactions, some fatal, have been reported Idamycin PFS (Pfizer), Teva Pharmaceuticals, various; 20-mg
in association with this regimen. Patients experiencing a severe vials (1 mg/mL) as powder for reconstitution; 5-, 10-, 20-mg
cutaneous or mucocutaneous reaction should not receive any vials (1 mg/mL) of preservative-free solution
further component of this therapeutic regimen and should seek
prompt medical evaluation. The prescribed, measured, and admin-
istered dose of Y-90 ibritumomab tiuxetan should not exceed the Indications: AML (in combination)
absolute maximum allowable dose of 32.0 mCi (1,184 MBq). Y-90 Mode & Vehicle of Administrationa,b: I.V. injection over 10-15 min-
ibritumomab tiuxetan should not be administered to patients with utes into the tubing of a freely running I.V. infusion of NS or D5W.
altered biodistribution as determined by imaging with In-111 ibritu-
Usual Single-Agent Dose Rangec-e: 12 mg/m2 daily for 3 days by
momab tiuxetan.
A
slow infusion (in combination with cytarabine). Dosage reduction
ll
Comments—AEs were followed for 12 weeks after the first ritux- for hepatic or renal dysfunction may be considered.
ri
gh
Co es
imab infusion.
Special Precautions/Instructions: Precipitation occurs when mixed
ts
py erv
Extravasation Category: Warning against extravasation with heparin. Treat extravasation with intermittent ice packs. Do
ri
gh d.
Handle as Hazardous Drugh: No data not administer IM or SQ. Pregnancy category D.
t
© ep
Toxicitiesf,g:
2 0 ro
All Grades of Toxicity—Infections; nausea/vomiting; hair loss;
08 du
abdominal cramps/diarrhea; hemorrhage; mucositis; dermatologic,
M tio
mental status, pulmonary (clinical) effects; fever; headache; cardiac
cM n
(clinical), neurologic (peripheral nerves), pulmonary effects; allergy;
ah in
c
seizure; cerebellar toxicity
on w
Pu ol
Boxed Warning—Should never be given IM or SQ. Severe local
bl e o
tissue necrosis if extravasation occurs during administration; can
is
h
cause myocardial toxicity leading to CHF; severe myelosuppression
hi
ng n p
occurs. Dosage should be reduced in patients with impaired renal
or hepatic function.
G art
i
ro
up wit
un ho
le ut
ss
ot rm
he
pe
rw sio
is
is
e
no s p
n
t e ro h
i
d. ib
tei
d.

Ifosfamide Interferon alfa-2a (recombinant)

Ifex (Bristol-Myers Squibb), Teva Pharmaceuticals, various; Roferon-A (Roche Pharmaceuticals); solution for injection:
injectable 1-, 3-g vials 3–, 6–, 9–million IU single-use prefilled syringes
Indications: Third-line treatment of germ cell testicular cancer Indications: Hairy cell leukemia in patients aged ≥18 years; Ph+
(in combination) CML in patients who are minimally pretreated (within 1 year of
Mode & Vehicle of Administrationa,b: I.V. infusion over a mini- diagnosis); chronic hepatitis C in patients aged ≥18 years
mum of 30 minutes. Mode & Vehicle of Administrationa,b: SQ, IM (data are limited)
Usual Single-Agent Dose Rangec-e: 1.2 g/m2/d × 5 days. Usual Single-Agent Dose Rangec-e: Hairy cell leukemia: induction,
3 million IU daily × 16-24 weeks; maintenance, 3 million IU tiw.
A
Special Precautions/Instructions: Administer with mesna
ll
(Mesnex, Bristol-Myers Squibb Oncology) I.V. and maintain
ri
CML: 9 million IU SQ or IM daily.
gh
Co es
adequate hydration to prevent hemorrhagic cystitis. Pregnancy
Special Precautions/Instructions: Pregnancy category C.
ts
py erv
category D.
ri
Toxicitiesf,g:
gh d.
f,g
Toxicities :
t
All Grades of Toxicity (≥5%)—Fever, asthenia or fatigue, myalgia,
© ep
All Grades of Toxicity (>1%)—Alopecia, nausea/vomiting, hema-
e
chills, arthralgia/bone pain, headache, anorexia, nausea/vomiting,
2 0 ro
turia, gross hematuria, CNS toxicity, infection, renal impairment,
R
diarrhea, depression, decreased mental status, dizziness, sleep dis-
08 du
liver dysfunction, phlebitis, fever, myelosuppression, leukopenia,
turbances, paresthesia, involuntary movements, visual disturbance,
M tio
thrombocytopenia
coughing, dyspnea, dysrhythmia, hair changes (including alopecia),
cM n
Boxed Warning—Urotoxic side effects and CNS toxicities have skin rash, sweating, dry skin, pruritus, weight loss, arthritis or poly-
ah in
c
been associated with use of ifosfamide; severe myelosuppression arthritis, throat irritation, rhinorrhea, sinusitis, pneumonia, anxiety,
on w
has been reported. confusion, chest pain, edema, HTN, pain, back pain, numbness
Pu ol
bl e o
Extravasation Category: Irritant Boxed Warning—Can cause or aggravate life-threatening neuro-
is
h
psychiatric, autoimmune, ischemic, and infectious disorders.
hi
ng n p
Comments—Dose reduction and temporary cessation of therapy
G art
were required frequently.
ro
up wit
un ho
Handle as Hazardous Drugh: Yes1-3,5
le ut
ss
ot rm
he
pe
rw sio
is
is
e
no s p
n
t e ro h
i
d. ib
tei
d.

Interferon alfa-2b (recombinant) Irinotecan

Intron-A (Schering); powder for injection: 10, 18, 50 million–IU Camptosar (Pfizer Oncology), Teva Pharmaceuticals; 40-mg/
vials; solution for injection: 10 million–IU single-dose vials, 2-mL, 100-mg/5-mL vials of injectable solution
18, 25 million–IU multidose vials, 18, 30, 60 million–IU prefilled
multidose pens Indications: Component of first-line therapy in combination with
5-FU and leucovorin for patients with metastatic carcinoma of the
Indications: In patients aged ≥18 years: hairy cell leukemia, colon or rectum; metastatic carcinoma of the colon or rectum in
adjuvant treatment of malignant melanoma (disease-free patients at patients with disease that has recurred or progressed following
risk for recurrence within 56 days of surgery), clinically aggressive 5-FU–based therapy
follicular NHL (in conjunction with anthracycline-containing chemo- Mode & Vehicle of Administrationa,b: I.V. infusion over 90 minutes.
A
therapy), condylomata acuminata, AIDS-related Kaposi’s sarcoma,
ll
Usual Single-Agent Dose Rangec-e: Combination therapy: 125
chronic hepatitis C; in patients aged ≥1 year: chronic hepatitis B
ri
mg/m2 on days 1, 8, 15, 22 of a 6-week cycle or 180 mg/m2 on days
gh
Co es
Mode & Vehicle of Administrationa,b: IM; SQ; intralesional; I.V. in
ts
py erv
1, 15, 29 of a 6-week cycle; refer to PI for subsequent doses.
r
100 mL NS to infuse over 20 minutes.
ri
Single-agent therapy: 125 mg/m2 on days 1, 8, 15, 22 of a 6-week
gh d.
Usual Single-Agent Dose Rangec-e: Hairy cell leukemia: 2 million IU/ cycle or 350 mg/m2 once every 3 weeks.
t
© ep
m2 IM or SQ tiw; improvement may require 6 months of treatment.
e
Special Precautions/Instructions: Pretreat with 5-HT3 blocker
2 0 ro
Kaposi’s sarcoma: 30 million IU/m2 IM or SQ tiw.
R
and dexamethasone to prevent emesis. Early diarrhea and late
08 du
Condylomata acuminata: 1 million IU into each lesion tiw on alter- diarrhea occur. Early diarrhea occurs within the first 24 hours and
M tio
nate days × 3 weeks; additional course may be given at 12-16
cM n
can be treated with 0.25 to 1 mg atropine. Late diarrhea can be life
weeks.
ah in
threatening. This occurs >24 hours after treatment. At first onset
c
Hepatitis B (adults): 30-35 million IU weekly SQ or IM, either as
on w
of late diarrhea, give 4 mg loperamide followed by 2 mg every
5 million IU/d or as 10 million IU tiw × 16 weeks. 2 hours until patient is diarrhea-free for 12 hours. Genetic testing
Pu ol
Malignant melanoma: 20 million IU/m2/d I.V. infusion × 5 con- can identify patients with the UGT1A1*28 polymorphism (~10% of
bl e o
secutive days/wk × 1 month, followed by 10 million IU/m2 SQ tiw
is
h
patients), who are at an increased risk for toxicity. Pregnancy cat-
hi
× 48 weeks. egory D.
ng n p
Follicular lymphoma: 5 million IU SQ tiw up to 18 months.
r
Toxicitiesf,g:
G art
i
ro
Hepatitis C: 3 million IU SQ or IM tiw up to 24 months.
up wit
Grade 3 or 4 Toxicity—Diarrhea (late and early), nausea, abdom-
Special Precautions/Instructions: Patient should be well hydrated. inal pain, vomiting, anorexia, mucositis, neutropenia, leukopenia,
un ho
Pregnancy category C.
anemia, neutropenic fever, thrombocytopenia, neutropenic infec-
le ut
f,g
Toxicities :
ss
tion, asthenia, pain, elevated bilirubin, dyspnea, pneumonia, dizzi-
ot rm
All Grades of Toxicity (≥5%)—Application site disorders, ness, somnolence, hypotension
he
fever, headache, chills, myalgias, fatigue, sweating increased,
pe
Boxed Warning—Can induce both early and late forms of diar-
rw sio
asthenia, arthralgias, dizziness, flulike symptoms, back pain, rhea; both forms may be severe.
is
dry mouth, pain (unspecified), diarrhea, anorexia, nausea, taste
is
e
no s p
alteration, vomiting, depression, paresthesia, dermatitis, alope-
t e ro h
cia, pruritus, rash, dry skin, abnormal ALT, anxiety, facial edema, Handle as Hazardous Drugh: Yes1-5
d.
weight decrease, rigors, chest pain, abdominal pain, constipa-
tion, confusion, insomnia, nasal congestion, dyspnea, coughing,
pharyngitis, sinusitis, moniliasis
ib
tei
Boxed Warning—Can cause or aggravate fatal or life-threatening
d.
neuropsychiatric, autoimmune, ischemic, and infectious disorders.
Comments—Most AEs were mild to moderate in severity and
were manageable. Some were transient and diminished with
continued therapy.
Handle as Hazardous Drugh: Yes1-3,5

Ixabepilone Leuprolide
Ixempra (Bristol-Myers Squibb); 15-, 45-mg vials in kits Lupron (TAP Pharmaceuticals), Teva Pharmaceuticals; 5 mg/
with diluent mL, 2.8 mL in multidose vial with syringes in 14-day kit; Lupron
Depot: 7.5-, 22.5-, 30-mg prefilled dual-chamber syringes;
Indications: In combination with capecitabine for metastatic or Lupron Depot-Ped: 7.5-, 11.25-, 15-mg prefilled dual-chamber
locally advanced breast cancer after failure of an anthracycline and syringes
a taxane; as monotherapy for metastatic or locally advanced breast Eligard (Sanofi-Aventis); 7.5-, 22.5-, 30-, 45-mg suspension for
cancer after failure of an anthracycline, a taxane, and capecitabine injection
Mode & Vehicle of Administrationa,b: I.V. infusion over 3 hours, Viadur (Bayer); 72-mg implant (65 mg leuprolide base)
administered through an in-line microporous membrane of 0.2-1.2
A
μm. Bag, tubing, and filter should be DEHP-free.
ll
Indications: All forms: palliative treatment of advanced prostate
ri
Usual Single-Agent Dose Rangec-e: 40 mg/m2 every 21 days.
gh
Co es
cancer; Lupron Depot-Ped only: central precocious puberty
ts
py erv
Special Precautions/Instructions: Patients should be premedi- (concomitantly with iron therapy for anemia caused by uterine
ri
cated approximately 1 hour before infusion with an H1 and H2 leiomyomata)
gh d.
receptor antagonist. Patients who experience a hypersensitivity
t
Mode & Vehicle of Administrationa,b: Lupron: SQ for daily dosing;
© ep
e
reaction require premedication with steroids as well as an H1 and IM for depot suspension dosing.
2 0 ro
H2 receptor antagoinst. Do not administer to patients who have
08 du
had a severe reaction to Cremophor EL. Dose for patients with Eligard: SQ for depot suspension dosing.
M tio
a BSA >2.2 m2 should be calculated based on a BSA of 2.2 m2. Viadur: SQ
cM n
Pregnancy category D. Usual Single-Agent Dose Rangec-e: Advanced prostate cancer:
ah in
c
Toxicitiesf,g:
on w
1 mg SQ daily.
Pu ol
Grade 3 or 4 Toxicity (>1%)—Neutropenia, neutropenic fever, leu- Depot form given as 7.5 mg every month, 22.5 mg every 3 months,
bl e o
kopenia, anemia, thrombocytopenia, anorexia, peripheral neuropa- 30 mg every 4 months, or (Eligard only) 45 mg every 6 months.
is
h
hi
thy, nausea, stomatitis/mucositis, constipation, abdominal pain, Implant: 65 mg every 12 months.
ng n p
skin rash, palmar–planter erythrodysesthesia syndrome, myalgia/
Special Precautions/Instructions: Pregnancy category X.
G art
arthralgia, musculoskeletal pain, fatigue/asthenia, pain
ro
Toxicitiesf,g:
up wit
Boxed Warning—Ixabepilone in combination with capecitabine is
contraindicated in patients with AST or ALT >2.5 × the upper limit All Grades of Toxicity (≥2%)—Asthenia, hot flashes/sweats,
un ho
of normal or bilirubin above the upper limit of normal because of
le ut
headache, extremity pain, diarrhea, ecchymosis, anemia, periph-
ss
increased risk for toxicity and neutropenia-related death. eral edema, weight gain, depression, dyspnea, sweating, alopecia,
ot rm
Comments—See PI for dose adjustments after toxicity or with gynecomastia/breast enlargement, nocturia, urinary frequency,
he
breast pain, impotence, decreased libido, testicular atrophy or
pe
administration of strong CYP3A4 inhibitors.
rw sio
pain, clamminess, nausea
is
is
e
No Boxed Warning
no s p
t e ro h
d.
Handle as Hazardous Drugh: Yes2,3,5
ib
tei
d.

Mechlorethamine Melphalan
Mustargen (Ovation Pharmaceuticals); injectable 10 mg/vial Alkeran (Celgene Corp); 2-mg tablets; injectable 50-mg vial
Indications: I.V.: palliative treatment of Hodgkin’s disease (stages Indications: Palliative treatment of multiple myeloma; palliation of
III and IV), lymphosarcoma, chronic myelocytic leukemia, CLL, nonresectable epithelial carcinoma of the ovary
polycythemia vera, mycosis fungoides, bronchogenic carcinoma Mode & Vehicle of Administrationa,b: PO; injectable (given over
Intrapleural, intraperitoneal, or intrapericardial: palliative treatment at least 15 minutes, completed within 1 hour).
of metastatic carcinoma resulting in effusion Usual Single-Agent Dose Rangec-e: Multiple myeloma: 6 mg/d
Mode & Vehicle of Administrationa,b: I.V. push over 1-3 minutes PO × 2-3 weeks. Subsequent courses depend on recovery from
into tubing of a rapidly running I.V. solution; intracavitary. previous course.
A
ll
Usual Single-Agent Dose Rangec-e: 0.4 mg/kg per course (single Ovarian carcinoma: 0.2 mg/kg/d PO × 5 days, repeat every 4-5
ri
gh
Co es
dose or divided doses). Dose based on ideal body weight. weeks.
ts
py erv
Special Precautions/Instructions: Treat extravasation by infiltrat- I.V. dosing: 16 mg/m2 every 2-3 weeks × 4 doses, then every 4 weeks.
ri
gh d.
ing the area with sodium thiosulfate (1⁄6 molar) and applying ice Special Precautions/Instructions: Administration of live vaccines
t
compress for 6-12 hours. Pregnancy category D.
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to immunocompromised patients should be avoided. Pregnancy
2 0 ro
Toxicitiesf,g: category D.
08 du
All Grades of Toxicity—Thrombosis, thrombophlebitis, hyper- Toxicitiesf,g:
M tio
sensitivity reaction (including anaphylaxis), nausea, vomiting,
cM n
All Grades of Toxicity—Bone marrow suppression, leukopenia,
depression of formed elements in circulating blood, jaundice,
ah in
c
thrombocytopenia, nausea, vomiting, diarrhea, oral ulceration,
alopecia, vertigo, tinnitus, diminished hearing, hemolytic anemia,
on w
hepatic disorders (ranging from liver function test abnormalities
chromosomal abnormalities, lymphocytopenia, granulocytopenia,
Pu ol
to clinical manifestations such as hepatitis and jaundice), hepatic
agranulocytosis, thrombocytopenia that may lead to bleeding
bl e o
veno-occlusive disease, acute hypersensitivity, anaphylaxis (urti-
from the gums and GI tract, petechiae, small SQ hemorrhages,
is
h
caria, pruritus, edema, tachycardia, bronchospasm, dyspnea,
hi
pancytopenia, hyperheparinemia, maculopapular skin eruption,
ng n p
hypotension), pulmonary fibrosis, interstitial pneumonitis, skin
erythema multiforme, herpes zoster, delayed catamenia, oligo- hypersensitivity, vasculitis, alopecia, hemolytic anemia, skin ulcer-
G art
menorrhea, amenorrhea, impaired spermatogenesis, azoospermia,
ro
ation at injection site, skin necrosis
up wit
total germinal aplasia
Boxed Warning—Severe bone marrow suppression with resulting
un ho
Boxed Warning—Highly toxic (corrosive, carcinogenic, mutagenic, infection or bleeding may occur; agent is leukemogenic in humans;
le ut
teratogenic); handle and administer with care; inhalation of dust produces chromosomal aberrations and should be considered
ss
or vapors and contact with skin or mucous membranes, especially potentially mutagenic in humans; hypersensitivity reactions, includ-
ot rm
those of the eyes, must be avoided; avoid exposure during preg-
he
ing anaphylaxis, have occurred in approximately 2% of patients
pe
nancy; extravasation into SQ tissues results in painful inflammation.
rw sio
who received I.V. formulation.
is
is
Comments—More myelosuppression with I.V. formulation than
e
no s p
Handle as Hazardous Drugh: Yes1-5 with oral formulation.
t e ro h
i
d.
ib
tei
d.

necrosis, erythema multiforme, pruritus, urticaria, photosensitivity,

Methotrexate pigmentary changes, alopecia, ecchymosis, telangiectasia, acne,
Various, 2.5-, 5-, 7.5-, 10-, 15-mg tablets; 25-mg/mL vials; furunculosis, erythematous rashes, nephropathy, acute renal fail-
10-, 25-mg/mL preservative-free single-use vials; lyophilized ure, azotemia, cystitis, hematuria, proteinuria, defective oogenesis
powder for injection 1-g vials or spermatogenesis, transient oligospermia, menstrual dysfunction,
vaginal discharge, gynecomastia, infertility, abortion, fetal defects
or death, gingivitis, pharyngitis, anorexia, hematemesis, melena, GI
Indications: Gestational choriocarcinoma, chorioadenoma ulceration/bleeding, enteritis, pancreatitis, conjunctivitis, serious
destruens, hydatidiform mole; meningeal leukemia (injection only); visual changes, pericarditis, pericardial effusion, hypotension,
prophylaxis of meningeal leukemia in acute lymphocytic leukemia; thromboembolic events (arterial thrombosis, cerebral thrombo-
breast cancer; epidermoid cancers of the head and neck; advanced sis, DVT, retinal vein thrombosis, thrombophlebitis, pulmonary
mycosis fungoides; lung cancer; advanced-stage NHL (in combina- embolus), malaise, undue fatigue, chills, dizziness, decreased infec-
A
tion); nonmetastatic osteosarcoma in patients who have had surgi-
ll
tion resistance, nodulosis, vasculitis, arthralgia/myalgia, loss of
ri
cal resection or amputation for the primary tumor (injection only) libido/impotence, diabetes, osteoporosis, sudden death, reversible
gh
Co es
Mode & Vehicle of Administrationa,b: PO; intra-arterial; IM; IT; I.V. lymphomas, tumor lysis syndrome, soft tissue necrosis, osteo-
ts
py erv
r
necrosis, anaphylactoid reactions
ri
push; I.V. infusion in up to 500 mL.
gh d.
Usual Single-Agent Dose Rangec-e: Trophoblastic diseases: 15-30 Boxed Warning—Has been reported to cause fetal death and/
t
© ep
mg PO or IM daily × 5 days; repeat 3-5 times, as required; ≥1 week
e
or congenital anomalies; unexpectedly severe (sometimes fatal)
2 0 ro
rest period between courses. bone marrow suppression, aplastic anemia, and GI toxicity have
08 du
been reported; causes hepatotoxicity, fibrosis, and cirrhosis after
Lymphocytic leukemia: (induction) 3.3 mg/m2/d × 4-6 weeks in
M tio
prolonged use; acutely, liver enzyme elevations are frequently
cM n
combination with other agents; (remission) 30 mg/m2 PO or IM
seen; methotrexate-induced lung disease is a potentially danger-
ah in
total weekly dose or 2.5 mg/kg/d I.V. every 2 weeks.
c
ous lesion; diarrhea and ulcerative stomatitis require interruption
on w
Meningeal leukemia: 12 mg/m2 IT over 2-5 days. of therapy; malignant lymphomas may occur; may induce tumor
Pu ol
Lymphomas: 10-25 mg/d PO × 4-8 days. lysis syndrome; severe, occasionally fatal skin reactions have been
bl e o
reported; potentially fatal opportunistic infections may occur;
is
h
Mycosis fungoides: 5-50 mg PO once weekly, 15-37.5 mg PO twice
hi
methotrexate given concomitantly with radiotherapy may increase
ng n p
weekly. risk for soft tissue necrosis and osteonecrosis. Methotrexate elimi-
G art
Osteosarcoma: 1,200 mg/m2 I.V., IM, or PO over 4 hours in combination is decreased in patients with impaired renal function, ascites,
ro
nation with other agents. or pleural effusions.
up wit
Special Precautions/Instructions: Person administering metho- Extravasation Category: Irritant
un ho
le ut
trexate must be thoroughly familiar with leucovorin rescue process. Handle as Hazardous Drugh: Yes1-5
ss
Do not exceed 15 mg IT. Leucovorin must not be administered IT.
ot rm
Pregnancy category X.
he
pe
Toxicitiesf,g:
rw sio
is
All Grades of Toxicity—Vomiting, diarrhea, ulcerative stomati-
is
e
no s p
tis, nausea, abdominal distress, dehydration, anemia, leukopenia,
t e ro h
thrombocytopenia, elevated transaminase, fibrosis, cirrhosis, dis-
d.
seminated vaccinia infections, hypogammaglobulinemia, oppor-
tunistic infections, focal seizures, acute neurologic syndrome
(confusion, hemiparesis, transient blindness, seizures, coma),
ib
i
acute chemical arachnoiditis (headache, back pain, nuchal rigid-
te
d.
ity, fever), subacute myelopathy (paraparesis/paraplegia), chronic
leukoencephalopathy (confusion, irritability, somnolence, ataxia,
dementia, seizure, coma), drowsiness, blurred vision, aphasia,
cognitive dysfunction, mood alteration, unusual cranial sensations,
leukoencephalopathy, encephalopathy, cough, pneumonitis, fever,
dyspnea, hypoxemia, infiltrates, interstitial COPD, toxic epidermal
necrolysis, Stevens-Johnson syndrome, exfoliative dermatitis, skin

Mitomycin-C Mitoxantrone
Various; injectable 5-, 20-, 40-mg vials Mitotane
Novantrone (EMD Serono Inc), Teva Pharmaceuticals, various;
concentrate for injection Squibb
Lysodren (Bristol-Myers 20-, 25-,Oncology)
30-mg vials
500-mg tablets
Indications: Disseminated adenocarcinoma of the stomach or
pancreas (in combination) Indications: Acute nonlymphocytic leukemias (combination ini-
Mode & Vehicle of Administrationa,b: I.V. tial therapy in adults); pain from advanced hormone-refractory
Usual Single-Agent Dose Rangec-e: 20 mg/m2 as a single dose prostate cancer (in combination with corticosteroids); secondary
repeated every 6-8 weeks. (chronic) progressive, progressive relapsing, or worsening relaps-
ing-remitting multiple sclerosis
Special Precautions/Instructions: Extravasation must be avoided.
Severe tissue ulceration can occur if drug is delivered outside the Mode & Vehicle of Administrationa,b: I.V. infusion over at least
A
3 minutes.
ll
vein. Pregnancy category D.
ri
Usual Single-Agent Dose Rangec-e: Leukemia: 12 mg/m2/d, days
gh
Co es
f,g
Toxicities :
ts
py erv
1-3 (combination therapy).
All Grades of Toxicity—Thrombocytopenia, leukopenia, cellulitis,
ri
Prostate cancer: 12-14 mg/m2 every 21 days.
gh d.
stomatitis, alopecia, rashes, necrosis upon extravasation, delayed
t
erythema and ulceration, rise in creatinine, dyspnea, cough, pul- Special Precautions/Instructions: Incompatible with heparin-
© ep
e
monary infiltrates, ARDS, hemolytic-uremic syndrome (micro- containing solutions. Pregnancy category D.
2 0 ro
R
angiopathic hemolytic anemia, pulmonary edema, neurologic
08 du
Toxicitiesf,g:
abnormalities, HTN), CHF, fever, anorexia, nausea, vomiting, head-
M tio
All Grades of Toxicity (≥5%)—Decreased WBC, granulocytes/
cM n
ache, blurring of vision, confusion, drowsiness, syncope, fatigue,
bands, decreased hemoglobin, lymphocytes, pain, platelets,
ah in
edema, thrombophlebitis, hematemesis, diarrhea, pain, malaise,
c
changes in ALK-P, malaise/fatigue, hyperglycemia, edema,
on w
asthenia, bladder fibrosis/contraction
nausea, anorexia, changes in BUN, transaminase, alopecia, car-
Pu ol
Boxed Warning—Bone marrow suppression, which may contribute diac function, infection, weight loss, dyspnea, diarrhea, fever in
bl e o
to overwhelming infection, is the most common and severe of the absence of infection, weight gain, abnormal creatinine, other GI
is
h
hi
toxic effects; hemolytic-uremic syndrome has been reported. symptoms, vomiting, other neurologic symptoms, hypocalcemia,
ng n p
Extravasation Category: Vesicant hematuria, hyponatremia, sweats, other liver symptoms, stomati-
G art
tis, cardiac dysrhythmia, hypokalemia, neuro/constipation, neuro/
ro
up wit
motor, neuro/mood, skin, cardiac ischemia, chills, hemorrhage,
myalgias/arthralgias, other kidney/bladder symptoms, other
un ho
endocrine symptoms, other pulmonary symptoms, impotence/
le ut
ss
decreased libido, proteinuria, sterility
ot rm
Boxed Warning—Never administer intra-arterially, IM, IT, or SQ;
he
pe
severe local tissue damage if extravasation occurs during adminis-
rw sio
tration; can cause bone marrow suppression, which may be severe
is
is
e
and result in infection; cardiotoxicity may occur either during ther-
no s p
apy or months to years after termination of therapy and is associ-
t e ro h
ated with cumulative doses greater than 140 mg/m2; secondary
d.
AML has been reported and is more common when anthracyclines
are given in combination with DNA-damaging antineoplastics,
ib
when patients have been heavily pretreated with cytotoxics, and
tei
when doses of anthracyclines have been escalated.
d.
Comments—These AEs were reported when mitoxantrone was
given in combination with hydrocortisone.

Oxaliplatin Paclitaxel
Eloxatin (Sanofi-Aventis); preservative-free aqueous solution in Taxol (Bristol-Myers Squibb), Teva Pharmaceuticals, various;
50-mg/10-mL, 100-mg/120-mL, 200-mg/140-mL 30-mg/5-mL, 100-mg/16.7-mL, 150-mg/25-mL, 300-mg/50-mL
multiple-dose vials
Indications: In combination with infusional 5-FU/leucovorin for
adjuvant treatment of stage III colon cancer in patients who have Indications: First-line therapy combined with cisplatin for
undergone complete resection of the primary tumor; in combination advanced ovarian carcinoma; adjuvant treatment of node-
with infusional 5-FU/leucovorin for treatment of advanced carci- positive breast cancer administered sequentially with standard
noma of the colon or rectum doxorubicin-containing regimen; treatment of breast cancer after
Mode & Vehicle of Administrationa,b: I.V. infusion over 120 failure of combination chemotherapy for metastatic disease or
A
relapse within 6 months of adjuvant chemotherapy; second-line
ll
minutes in 250-500 mL D5W.
ri
treatment of AIDS-related Kaposi’s sarcoma; first-line treat-
gh
Usual Single-Agent Dose Rangec-e: 85 mg/m2 on day 1, once
Co es
ment combined with cisplatin for NSCLC in patients who are not
ts
py erv
every 2 weeks.
candidates for potentially curative surgery or radiation therapy
ri
Special Precautions/Instructions: Reconstitution or final dilu-
gh d.
Mode & Vehicle of Administrationa,b: I.V.: dilute to 0.3-1.2 mg/mL
t
tion must never be performed with chloride-containing solutions.
in NS, D5W, or D5 Ringer’s. Given I.V. over 3-24 hours.
© ep
e
Aluminum-containing needles or I.V. administration sets should
2 0 ro
not be used. Premedication with antiemetics is recommended. Usual Single-Agent Dose Rangec-e: Ovarian carcinoma: 135 mg/
08 du
Pregnancy category D. m2 over 24 hours, or 175 mg/m2 over 3 hours, every 3 weeks.
M tio
Patients previously treated with chemotherapy for ovarian cancer:
cM n
f,g
Toxicities :
135 mg/m2 or 175 mg/m2 over 3 hours every 3 weeks.
ah in
c
Grade 3 or 4 Toxicity (≥1%)—Fatigue, neuropathy, abdominal
on w
Node-positive breast cancer: 175 mg/m2 over 3 hours every 3
pain, dyspnea, diarrhea, nausea, vomiting, pain, dehydration,
weeks for 4 courses.
Pu ol
anorexia, hypokalemia, fever, edema, thromboembolism, chest
bl e o
pain, anemia, thrombocytopenia, liver abnormalities (ALT, AST, Metastatic breast cancer: 175 mg/m2 over 3 hours every 3 weeks.
is
h
Kaposi’s sarcoma: 135 mg/m2 over 3 hours every 3 weeks or
hi
total bilirubin)
ng n p
100 mg/m2 over 3 hours every 2 weeks.
Boxed Warning—Anaphylaxis-like reactions have been reported,
G art
NSCLC: 135 mg/m2 over 24 hours every 3 weeks.
i
and epinephrine, corticosteroids, and antihistamines have been
ro
up wit
used to alleviate symptoms. Special Precautions/Instructions: Prepare in glass, polyolefin, or
un ho
Extravasation Category: Vesicant polypropylene containers. Infusion solution must be administered
le ut
through a 0.22-μm in-line filter using non-PVC tubing. Pregnancy
ss
category D.
ot rm
Toxicitiesf,g:
he
pe
rw sio
Grade 3 or 4 Toxicity—Myalgia/arthralgia, peripheral neuro-
is
pathy, hypersensitivity reactions, CV events, neutropenia, leuko-
is
e
no s p
penia, anemia, thrombocytopenia
t e ro h
Boxed Warning—Anaphylaxis and severe hypersensitivity
d.
reactions have occurred; bone marrow suppression may be severe
and result in infection. Pretreatment for hypersensitivity reaction
ib
with H2 blocker, corticosteroid, and diphenhydramine recommended.
tei
Comments—Frequency and severity of AEs generally similar in
d.
patients receiving paclitaxel for treatment of ovarian, breast, or
lung carcinoma or Kaposi’s sarcoma, but patients with AIDS-
related Kaposi’s sarcoma may have more frequent and severe
hematologic toxicity, infections, and febrile neutropenia.

Paclitaxel protein-bound particles Panitumumab

Abraxane (Abraxis Oncology); lyophilized powder for Vectibix (Amgen); 20 mg/mL in 5-, 10-, 20-mL single-use vials
reconstitution in 100-mg single-use vials
Indications: As monotherapy for EGFR-expressing metastatic
Indications: Breast cancer after failure of combination chemother- colorectal carcinoma with disease progression on or following
apy for metastatic disease or relapse within 6 months of adjuvant fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemo-
chemotherapy (prior therapy should have included an anthracy- therapy regimens
cline unless clinically contraindicated) Mode & Vehicle of Administrationa,b: Must be administered
Mode & Vehicle of Administrationa,b: I.V. infusion over 30 minutes. through a low–protein-binding 0.2- or 0.22-μm in-line filter. Doses
≤1,000 mg should be infused over 60 minutes; doses >1,000 mg
Usual Single-Agent Dose Rangec-e: 260 mg/m2 every 3 weeks.
A
should be infused over 90 minutes. Reduce infusion rate by 50%
ll
Special Precautions/Instructions: Contraindicated when abso- for grade 1 or 2 infusion reaction. Immediately and permanently
ri
gh
Co es
lute neutrophil count <1,500/mm3 or platelets <100,000/mm3. Do stop infusion for grade 3 or 4 infusion reaction. Do not administer
ts
py erv
not substitute for or with other paclitaxel forms. No drug inter- as I.V. push or bolus.
ri
action studies have been performed; however, paclitaxel is known
gh d.
Usual Single-Agent Dose Rangec-e: 6 mg/kg every 14 days. For
to be metabolized by CYP3A4 and CYP2C8. Caution should be
t
severe dermatologic reactions, hold dose until ≤grade 2 toxicity. If
© ep
e
used when administered with CYP3A4 and/or CYP2C8 induc- toxicity improves within 1 month, may restart at 50% of the original
2 0 ro
ers or inhibitors. If grade 3 sensory neuropathy develops, hold
R
dose. If toxicity recurs or resolution takes longer than 1 month, per-
08 du
dose until it resolves to grade 1 or 2 and reduce dose for next manently discontinue. If reduced dose is well tolerated, dose may
M tio
cycle. Hypersensitivity reactions have been reported. Patients
cM n
be increased by 25% increments.
who experience a severe hypersensitivity reaction should not be
ah in
c
rechallenged. Pregnancy category D. Special Precautions/Instructions: Patients should be advised to
on w
f,g wear sunscreen and hats and limit sun exposure as sunlight can
Toxicities :
Pu ol
exacerbate any skin reactions that may occur. EGFR testing should
bl e o
Incidence More Frequent (≥2% Grade 3-4 Toxicity)— demonstrate expression on the tumor surface. Magnesium and
is
h
hi
Neutropenia, febrile neutropenia, CV events, sensory neuropathy, calcium should be monitored during therapy and for 8 weeks after
ng n p
myalgia/arthralgia, asthenia, nausea, vomiting completion. May impair fertility, and nursing mothers should be
G art
Incidence Less Frequent—Hypersensitivity reactions, cardiac advised to discontinue nursing. Pregnancy category C.
ro
Toxicitiesf,g:
up wit
ischemia
un ho
Boxed Warning—Should not be administered to patients with Grade 3 or 4 Toxicity (≥1% higher than control)—Fatigue, gen-
le ut
metastatic breast cancer who have baseline neutrophil counts eral deterioration, abdominal pain, diarrhea, constipation, vomiting,
ss
<1,500/mm3. hypomagnesemia, skin effects (including erythema, acneiform der-
ot rm
matitis, pruritus, exfoliation, rash, skin fissures), paronychia
he
pe
rw sio
Handle as Hazardous Drugh: No data Boxed Warning—Dermatologic toxicity is common and severe in
is
12% of patients and can be associated with abscess or infection.
is
e
Withhold or discontinue treatment during severe dermatologic
no s p
n
reactions and monitor for infectious sequelae. Administration can
t e ro h
i
d.
result in severe infusion reactions in approximately 1% of patients.
Severe infusion reactions require immediate interruption of infusion
and, depending on the severity and duration, possible permanent
ib
discontinuation.
tei
d.
Comments—The use of premedications for infusion reactions has
not been studied and is not currently recommended.

Pegaspargase [PEG-L-asparaginase] Pemetrexed

Oncaspar (Enzon); preservative-free 5-mL single-dose vial, Alimta (Eli Lilly and Company); 100-, 500-mg single-use vials
750 IU/mL
Indications: As a single agent for the treatment of patients with
Indications: ALL in patients hypersensitive to native forms of locally advanced or metastatic NSCLC after prior chemotherapy;
L-asparaginase in combination with cisplatin for the treatment of patients with
malignant pleural mesothelioma whose disease is unresectable or
Mode & Vehicle of Administrationa,b: IM (preferred); I.V. infusion
who otherwise are not candidates for curative surgery
in 100 mL NS or D5W over 1-2 hours through an infusion that is
already running. IM injection should not exceed 2 mL at any single Mode & Vehicle of Administrationa,b: The reconstituted solution
site. should be further diluted to 100 mL with NS (preservative-free)
A
ll
Usual Single-Agent Dose Rangec-e: Adults and children ≥0.6 m2 and administered as an I.V. infusion over 10 minutes.
ri
BSA: 2,500 IU/m2 every 14 days.
gh
Co es
Usual Single-Agent Dose Rangec-e: NSCLC: 500 mg/m2 over
ts
py erv
Children <0.6 m2 BSA: 82.5 IU/kg every 14 days. 10 minutes on day 1 of each 21-day cycle.
ri
gh d.
Note: Only use as single agent when multiple-agent chemotherapy Pleural mesothelioma: 500 mg/m2 over 10 minutes on day 1 of
t
is judged to be inappropriate for the patient. each 21-day cycle, followed 30 minutes later by cisplatin.
© ep
e
2 0 ro
Special Precautions/Instructions: Hypersensitivity reaction and
Special Precautions/Instructions: Patients should receive vita-
08 du
anaphylaxis may occur. Contraindicated in patients with history of
min B12, folic acid, and dexamethasone (or equivalent) to reduce
M tio
serious hemorrhagic events on L-asparaginase, or previous serious
toxicity, according to the following schedules: 1,000 mcg vitamin
cM n
allergic reaction, pancreatitis, or history of pancreatitis. Causes
B12 IM during the week preceding the first dose of pemetrexed and
ah in
c
contact dermatitis; handle with care and use gloves. Pregnancy every 3 cycles thereafter; 350-1,000 mcg folic acid daily for at least
on w
category C. 5 days during the 7-day period preceding the first dose of pem-
Pu ol
Toxicitiesf,g: etrexed and continuing throughout therapy and for 21 days after
bl e o
is
the last dose of pemetrexed; dexamethasone 4 mg PO bid the day
h
All Grades of Toxicity—Allergic reactions (rash, erythema, edema,
hi
before, the day of, and the day after pemetrexed administration.
ng n p
pain, fever, chills, urticaria, dyspnea, bronchospasm), ALT increase,
nausea and/or vomiting, fever, malaise CBCs, including platelet counts, and periodic chemistry tests should
G art
i
be performed on all patients receiving pemetrexed. Patients should
ro
No Boxed Warning
up wit
not begin a new cycle of treatment unless the absolute neutrophil
Comments—Adult patients had a somewhat higher incidence of count is ≥1,500/mm3, the platelet count is ≥100,000/mm3, and
un ho
creatinine clearance is ≥45 mL/min. Dose adjustments at the start
le ut
known L-asparaginase toxicities, except for hypersensitivity reac-
ss
tions, than the pediatric patients treated. Other significant clinical of a subsequent cycle should be based on nadir hematologic counts
ot rm
events included clinical pancreatitis, hyperglycemia, and thrombosis. or maximum nonhematologic toxicity from the preceding cycle of
he
therapy. Avoid nonsteroidal anti-inflammatory drugs for at least 5
pe
rw sio
days before, the day of, and 2 days after pemetrexed administra-
is
Handle as Hazardous Drugh: Yes1-5 tion. Avoid in patients with a creatinine clearance of <45 mL/min.
is
e
no s p
Consider draining effusions prior to administration in patients with
t e ro h
clinically significant third-space fluid. Pregnancy category D.
d.
Toxicitiesf,g:
ib
Grade 3 or 4 Toxicity (>1% single-agent toxicity with recom-
tei
mended premedications)—Neutropenia, leukopenia, anemia,
d.
thrombocytopenia, elevated ALT, elevated AST, fatigue, fever,
myalgia, other constitutional symptoms, thromboembolism, car-
diac ischemia, anorexia, nausea, vomiting, dysphagia/esophagitis/
odynophagia, dyspnea, chest pain, sensory neuropathy, infection
with or without neutropenia, febrile neutropenia
No Boxed Warning

Comments—Dose reductions for grade 3/4 toxicity are outlined

in the PI. For severe hematologic toxicity, leucovorin was allowed Rituximab
in clinical trials. Rare cases of colitis have been reported with post- Rituxan (Biogen Idec/Genentech BioOncology);
marketing surveillance. In patients 65 years or older, the incidence 100-mg/10-mL and 500-mg/50-mL single-use vials
of grade 3/4 HTN has been reported more frequently than in
younger patients. Indications: Relapsed or refractory, low-grade or follicular, CD20-
Extravasation Category: Nonvesicant positive B-cell NHL; follicular, CD20-positive B-cell NHL as first-line
treatment in combination with CVP chemotherapy; low-grade,
Handle as Hazardous Drugh: No data CD20-positive B-cell NHL in patients with stable disease or who
achieve a partial or complete response following first-line treat-
ment with CVP chemotherapy; diffuse large B-cell, CD20-positive
A
NHL as first-line treatment in combination with CHOP or other
ll
anthracycline-based chemotherapy regimens
ri
gh
Co es
Mode & Vehicle of Administrationa,b: I.V. infusion. First dose: begin
ts
py erv
at 50 mg/h and increase by 50 mg/h every 30 minutes to a maxi-
ri
gh d.
mum of 400 mg/h. For subsequent infusions, begin at 100 mg/h
t
and increase in increments of 100 mg/h. Maximum rate is 400
© ep
e
mg/h.
2 0 ro
R
08 du
Usual Single-Agent Dose Rangec-e: Relapsed or refractory, low-
M tio
grade or follicular, CD20-positive B-cell NHL: 375 mg/m2 I.V. week-
cM n
ly × 4 or 8 doses.
ah in
c
Previously untreated, follicular, CD20-positive B-cell NHL: 375 mg/
on w
m2 I.V. per infusion on day 1 of each cycle of CVP chemotherapy
Pu ol
for up to 8 doses.
bl e o
is
h
Previously untreated, low-grade, CD20-positive B-cell NHL: 375
hi
mg/m2 I.V. weekly × 4 doses every 6 months for up to 16 doses.
ng n p
r
Diffuse large B-cell NHL: 375 mg/m2 I.V. per infusion on day 1 of
G art
i
ro
each cycle of chemotherapy for up to 8 infusions.
up wit
Special Precautions/Instructions: Because of the potential for
un ho
allergic infusion-related reactions, consider premedication of each
le ut
ss
dose with acetaminophen and diphenhydramine. If infusion-related
ot rm
events occur, temporarily slow or interrupt infusion. Once symp-
he
toms resolve, begin at half the previous rate. Reactivation of HBV
pe
rw sio
leading to fulminant hepatitis, hepatic failure, and death has been
is
reported. Screen persons at high risk for HBV infection before ini-
is
e
no s p
tiation of rituximab. Monitor carriers of hepatitis B during and for
t e ro h
up to several months after therapy. Discontinue therapy in patients
d.
who develop viral hepatitis. Additional serious viral infections have
been reported. Discontinue infusions in the event of serious or life-
threatening cardiac arrhythmias. Patients who develop clinically
ib
i
significant arrhythmias should undergo cardiac monitoring during
te
d.
and after subsequent infusions. Monitor patients with preexisting
cardiac conditions throughout the infusion and immediate post-
infusion period. Rituximab administration has been associated with
severe renal toxicity, including acute renal failure requiring dialysis,
in some cases fatal. Discontinuation of rituximab should be con-
sidered for those with rising serum creatinine or oliguria. Because
of the risk for bowel obstruction and perforation, complaints of

abdominal pain should prompt a thorough diagnostic evaluation

and appropriate treatment. Because rituxumab targets all CD20- Streptozocin
positive B lymphocytes (malignant and nonmalignant), perform Zanosar (Teva Pharmaceuticals); injectable 1-g vials
CBCs and platelet counts at regular intervals during therapy and
more frequently in patients who develop cytopenias. Pregnancy Indications: Metastatic islet cell carcinoma of the pancreas
category C.
f,g
Mode & Vehicle of Administrationa,b: Intra-arterial infusion not
Toxicities : recommended; should be given I.V. by rapid injection or short/pro-
Grade 3 or 4 Toxicity (>1%)—Chills, infection, lymphopenia, leuko- longed infusion.
penia, neutropenia, thrombocytopenia, anemia Usual Single-Agent Dose Rangec-e: 500 mg/m2/d for 5 consecu-
Boxed Warning—Fatal infusion reactions within 24 hours of ritux- tive days every 6 weeks, or 1 g/m2 weekly × 2 weeks, then increase
imab infusion have been reported. Discontinue infusion and initiate dose. Not recommended to exceed 1.5 g/m2 weekly.
A
ll
medical treatment in the event of severe infusion reactions. Acute Special Precautions/Instructions: Hypoglycemic reactions may
ri
gh
renal failure requiring dialysis with instances of fatal outcome has
Co es
result from sudden insulin release. Pregnancy category D.
ts
py erv
been reported in the setting of tumor lysis syndrome following
Toxicitiesf,g:
ri
treatment of NHL patients with rituximab. Severe mucocutane-
gh d.
ous reactions, some with fatal outcome, have been reported in All Grades of Toxicity—Azotemia, anuria, hypophosphatemia,
t
association with rituximab treatment. JC virus infection resulting in
© ep
glycosuria, renal tubular acidosis, nausea, vomiting, diarrhea,
2 0 ro
progressive multifocal leukoencephalopathy and death has been hepatic toxicity (elevated liver enzyme levels and hypoalbumin-
08 du
reported in patients treated with rituximab. emia), decreased hematocrit, leukopenia, thrombocytopenia,
M tio
Comments—Administration of rituximab weekly for 8 doses abnormalities of glucose tolerance, hypoglycemia with insulin
cM n
resulted in higher rates of grade 3 or 4 AEs than administration shock, nephrogenic diabetes insipidus, local inflammation upon
ah in
c
weekly for 4 doses. The incidence of grade 3 or 4 AEs in patients extravasation
on w
re-treated with rituxumab was similar to that in patients undergo- Boxed Warning—Renal toxicity is dose-related and cumulative
Pu ol
ing initial treatment. The incidence of abdominal pain, anemia, and may be severe or fatal; other major toxicities are nausea and
bl e o
dyspnea, hypotension, and neutropenia was higher in patients with vomiting, liver dysfunction, diarrhea, and hematologic changes;
is
h
hi
bulky disease. streptozocin is mutagenic and, when administered parenterally, has
ng n p
Extravasation Category: Nonirritant been found to be tumorigenic or carcinogenic in rodents.
G art
i
ro
Handle as Hazardous Drugh: No data Extravasation Category: Vesicant
up wit
un ho
le ut
ss
ot rm
he
pe
rw sio
is
is
e
no s p
n
t e ro h
i
d. ib
tei
d.

Temsirolimus Teniposide
Torisel (Wyeth); 25-mg/mL vials Vumon (Bristol-Myers Squibb Oncology); 50-mg/5-mL
injectable ampules
Indications: Advanced renal cell carcinoma
Mode & Vehicle of Administrationa,b: I.V. infusion over 30-60 Indications: Induction therapy (in combination) for refractory
minutes. childhood ALL
Usual Single-Agent Rangec-e: 25 mg weekly until disease Reconstitution, Chemical Stability, & Storage1,2: Diluted solution
progression or unacceptable toxicity. should not be refrigerated. Stable for 24 hours at concentrations
of 0.1 mg/mL, 0.2 mg/mL, and 0.4 mg/mL. Stable for 4 hours at
Special Precautions/Instructions: An in-line polyethersulfone
a concentration of 1 mg/mL. Refrigeration of solution not recom-
filter with a pore size of ≤5 μm is recommended for administration.
A
mended.
ll
Doses should be adjusted for neutrophil and platelet counts. See PI
ri
Mode & Vehicle of Administration3,4: Administer only by slow I.V.
gh
Co es
for details. Consider a dose adjustment when used in combination
ts
py erv
with a strong CYP3A4 inducer or inhibitor. Premedicate with an infusion (over at least 30-60 minutes).
ri
antihistamine (diphenhydramine 25-50 mg or similar) 30 minutes Usual Single-Agent Dose Range5-7: 165 mg/m2 in combination with
gh d.
before dosing. Pregnancy category D. cytarabine 300 mg/m2 I.V., twice weekly × 8-9 doses; 250 mg/m2
t
© ep
in combination with vincristine 1.5 mg/m2 I.V., weekly × 4-8 doses
e
Toxicitiesf,g:
2 0 ro
and prednisone 40 mg/m2 PO × 28 days.
08 du
Grade 3 or 4 Toxicity (≥2%)—HTN, fatigue, hand–foot skin reac-
tion, diarrhea, joint pain, lab abnormalities (hypophosphatemia, Special Precautions/Instructions: Do not give by rapid infusion.
M tio
cM n
increased lipase, lymphopenia, neutropenia) May cause hypotension. Observe patients for signs of hypersen-
ah in
sitivity reaction during infusion. Check solution before and during
c
Boxed Warning—Abdominal pain; anemia; anorexia; asthenia;
on w
administration for precipitation. Pregnancy category D.
back pain; decreased chemistry values for phosphorus and potas-
Pu ol
sium; dyspnea; edema; elevated chemistry values for ALK-P, AST, Toxicities8,9:
bl e o
cholesterol, creatinine, glucose, and triglycerides; infections; lym- All Grades of Toxicity (>1%)—Myelosuppression, leukopenia, neu-
is
h
hi
phopenia; mucositis; nausea; neutropenia; pain; rash; vomiting tropenia, thrombocytopenia, anemia, mucositis, diarrhea, nausea/
ng n p
Extravasation Category: Irritant vomiting, infection, alopecia, bleeding, hypersensitivity reactions,
G art
rash, fever, hypotension/CV effects
ro
up wit
Boxed Warning—Severe myelosuppression with resulting infec-
un ho
tion or bleeding may occur; hypersensitivity reactions, including
le ut
anaphylaxis-like reactions, may occur.
ss
ot rm
he
pe
rw sio
is
is
e
no s p
n
t e ro h
i
d. ib
tei
d.

Thiotepa Topotecan
Various; injectable 15-, 30-mg vials Hycamtin (GlaxoSmithKline); 4-mg (free base) single-dose
vials; 0.25-, 1-mg capsules
Indications: Palliation of adenoarcinoma of the breast and ovary;
superficial papillary carcinoma of the urinary bladder; controlling Indications: Injection: metastatic ovarian carcinoma after failure of
intracavitary effusions secondary to diffuse or localized neoplastic initial or subsequent chemotherapy; small-cell lung cancer sensitive
diseases of serosal cavities; lymphosarcoma and Hodgkin’s disease disease after failure of first-line chemotherapy; in combination with
(both now largely superseded by other treatments) cisplatin for stage IV-B, recurrent, or persistent carcinoma of the
Mode & Vehicle of Administrationa,b: I.V.; intracavitary; cervix that is not amenable to curative treatment with surgery and/
intravesical. or radiation therapy
A
Capsules: relapsed small-cell lung cancer
ll
Usual Single-Agent Dose Rangec-e: I.V.: 0.3- to 0.4-mg/kg bolus
ri
at 1- to 4-week intervals; intracavitary: 0.6-0.8 mg/kg; intravesi- Mode & Vehicle of Administrationa,b: I.V. infusion over at least
gh
Co es
cal (carcinoma of the bladder only): dehydrate patient for 8-12 30 minutes; PO.
ts
py erv
Usual Single-Agent Dose Rangec-e: Ovarian and small-cell lung
r
hours before treatment. Instill 60 mg in 30-60 mL NS into blad-
ri
gh d.
der by catheter. For maximum effect, retain solution for 2 hours. cancer: 1.5 mg/m2/d I.V. over 30 minutes, days 1-5 of a 21-day
t
Treatment course is once weekly × 4 weeks. course. A minimum of 4 courses is recommended.
© ep
e
2 0 ro
Special Precautions/Instructions: Repeat intravesical treatment if Cervical cancer (in combination with cisplatin): 0.75 mg/m2/d I.V.
08 du
necessary, but give second and third courses with caution, as bone over 30 minutes, days 1-3 of a 21-day course.
M tio
marrow depression may increase. Deaths—caused by bone marrow
cM n
Relapsed small-cell lung cancer: 2.3 mg/m2/d PO for 5 days every
depression from systemically absorbed drug—have occurred after
ah in
21 days.
c
intravesical use. Pregnancy category D.
on w
See PI for dose adjustments based on neutrophil and platelet
Toxicitiesf,g:
Pu ol
counts.
bl e o
All Grades of Toxicity—Leukopenia, thrombocytopenia, ane-
Special Precautions/Instructions: Reduce dose for renal dysfunc-
is
h
mia, fatigue, weakness, febrile reaction and discharge from SQ
hi
tion or severe neutropenia (see PI). Capsules should not be opened
ng n p
lesion, allergic reactions (rash, urticaria, laryngeal edema, asthma,
or crushed. If contents get on skin, wash with soap and water.
r
anaphylactic shock, wheezing), contact dermatitis, injection site
G art
Avoid concomitant use of P-glycoprotein inhibitors because they
ro
pain, nausea, vomiting, abdominal pain, anorexia, dysuria, urinary
up wit
increase topotecan exposure. Severe diarrhea that coincides with
retention, chemical cystitis, hemorrhagic cystitis, apnea, dizziness,
neutropenia has been reported. Pregnancy category D.
un ho
headache, blurred vision, dermatitis, alopecia, skin depigmentation,
le ut
conjunctivitis, amenorrhea, interference with spermatogenesis Toxicitiesf,g:
ss
Grade 3 or 4 Toxicity—Anemia, leukopenia, neutropenia, sepsis
ot rm
No Boxed Warning
he
or pyrexia/infection with neutropenia, thrombocytopenia, nausea,
pe
rw sio
diarrhea, vomiting, fatigue, anorexia, asthenia, dyspnea, constipa-
is
tion, abdominal pain, pain
is
e
no s p
Boxed Warning—To monitor bone marrow suppression, blood
t e ro h
cell counts should be monitored. Do not administer to patients
d.
with a baseline neutrophil count <1,500/mm3 or a platelet count
<100,000/mm3.
ib
Comments—Food does not affect bioavailability.
tei
d.

Tositumomab and iodine-131 tositumomab Trastuzumab

Toremifene
Bexxar (GlaxoSmithKline); supplied in 2 separate kits, one Herceptin (Genentech
Fareston (GTx, BioOncology);
Inc.) 60-mg tablets 440-mg vials
containing nonradioactive ingredients and the other containing
iodine-131–labeled antibody Indications: In combination with a doxorubicin-, cyclophos-
phamide-, and either paclitaxel- or docetaxel-containing regimen
Indications: Treatment of patients with CD20 antigen–expressing or with docetaxel and carboplatin for the adjuvant treatment of
relapsed or refractory low-grade follicular or transformed NHL HER2-overexpressing breast cancer; as a single agent for the adju-
whose disease is refractory to chemotherapy alone, to rituximab vant treatment of HER2-overexpressing breast cancer following
alone, or to chemotherapy and rituximab multimodality anthracycline-based therapy; in combination with
paclitaxel for HER2-overexpressing metastatic breast cancer; as
Mode & Vehicle of Administrationa,b: I.V. infusion.
A
a single agent for patients with HER2-overexpressing metastatic
ll
Usual Single-Agent Dose Rangec-e: The recommended dose is indi- breast cancer who have received 1 or more chemotherapy regi-
ri
gh
Co es
vidualized for each patient. Calculations for the therapeutic dose mens for their metastatic disease
ts
py erv
are made from the dosimetry dose.
Mode & Vehicle of Administrationa,b: I.V. infusion. Add dose to
ri
gh d.
Special Precautions/Instructions: Contraindicated for patients 250 mL NS (PVC or polyethylene bags). Do not administer as I.V.
t
with a known hypersensitivity to murine proteins. Thyroid-blocking push or bolus.
© ep
e
medications should be initiated at least 24 hours before the dosi-
Usual Single-Agent Dose Rangec-e: Adjuvant treatment (during
2 0 ro
metric dose and continued until 14 days after the therapeutic dose.
08 du
and after paclitaxel, docetaxel, or docetaxel-carboplatin and for a
Pregnancy category X.
M tio
total of 52 weeks): 4 mg/kg over 90 minutes, day 1, followed by 2
cM n
f,g
Toxicities : mg/kg over 30 minutes weekly during chemotherapy for the first
ah in
c
Grade 3 or 4 Toxicity (>1%)—Asthenia, fever, pain, chills, abdomi- 12 weeks (paclitaxel and docetaxel) or 18 weeks (docetaxel-carbo-
on w
nal pain, back pain, neck pain, hypotension, nausea, vomiting, platin); 1 week after the last weekly dose, administer 6 mg/kg over
Pu ol
constipation, arthralgia, increased cough, dyspnea, anemia, throm- 30-60 minutes every 3 weeks.
bl e o
bocytopenia, neutropenia Adjuvant treatment (after completion of all chemotherapy):
is
h
hi
Boxed Warning—Medications for the treatment of severe hyper- 8 mg/kg over 90 minutes, day 1, followed by 6 mg/kg over 30 min-
ng n p
sensitivity reactions should be available for immediate use. Patients utes every 3 weeks for a total of 52 weeks.
G art
i
who develop severe hypersensitivity reactions should have infu-
ro
Metastatic treatment (alone or in combination with paclitaxel):
up wit
sions of the tositumomab therapeutic regimen discontinued and 4 mg/kg over 90 minutes, day 1, followed by 2 mg/kg over
receive medical attention. The majority of patients who received
un ho
30 minutes weekly until disease progression.
le ut
the tositumomab therapeutic regimen experienced severe throm-
Special Precautions/Instructions: Store aqueous solution in
ss
bocytopenia and neutropenia. The tositumomab therapeutic regi-
vials under normal lighting conditions at 25°C. The solution
ot rm
men should not be administered to patients with >25% lymphoma
he
is further diluted in an infusion solution of 250-500 mL D5W.
marrow involvement and/or impaired bone marrow reserve.
pe
rw sio
After final dilution with D5W, the shelf life is 6 hours at room
Pregnancy category X. Health care professionals administering
is
temperature and up to 24 hours if refrigerated (2°-8°C). May
is
e
tositumomab need to be undergoing certification or be certified by
exacerbate chemotherapy-induced neutropenia and febrile neu-
no s p
GlaxoSmithKline in dose calculation and administration.
tropenia. Deaths due to sepsis in patients with severe neutropenia
t e ro h
i
Comments—Administration of tositumomab requires a high level
d.
have been reported in patients receiving trastuzumab and myelo-
of planning in order to coordinate the time of therapeutic dose suppressive chemotherapy, although in controlled clinical trials, the
administration. incidence of septic death was not significantly increased. Detection
ib
of HER2 protein overexpression is necessary for selection of
i
te
patients appropriate for trastuzumab therapy because these are
d.
Handle as Hazardous Drugh: No data the only patients studied and for whom benefit has been shown.
Pregnancy category B.
Toxicitiesf,g:
All Grades of Toxicity (≥5%)—Pain, asthenia, fever, chills, head-
ache, abdominal pain, back pain, infection, flu syndrome, accidental
injury, tachycardia, CHF, nausea, diarrhea, vomiting, anorexia,

peripheral edema, edema, bone pain, arthralgia, insomnia, dizzi-

ness, paresthesia, depression, cough increased, dyspnea, rhinitis, Triptorelin
pharyngitis, sinusitis, rash, UTI, fatigue, hot flashes, anemia, neutro- Trelstar Depot (Pfizer); 3.75-mg lyophilized microgranules for
penia, leukopenia, allergic reaction, peripheral neuritis, neuropathy, injection
herpes simplex, acne
Boxed Warning—Administration can result in LV dysfunction Indications: Advanced prostate cancer
and CHF, serious infusion reactions, and pulmonary toxicity. Mode & Vehicle of Administrationa,b: Single IM injection.
Discontinue in adjuvant setting and strongly consider discontinu-
ation in metastatic setting upon clinically significant decrease in Usual Single-Agent Dose Rangec-e: 3.75 mg repeated monthly.
LV function. Interrupt infusion in the case of dyspnea or clinically Special Precautions/Instructions: Hypersensitivity and anaphy-
significant hypotension. Discontinue in the case of anaphylaxis, lactic reactions have been reported. A temporary increase in
A
angioedema, pneumonitis, or ARDS. testosterone can be seen during the first week and may be associ-
ll
ated with worsening of disease signs and symptoms. Pregnancy
ri
gh
Co es
category X.
ts
py erv
Toxicitiesf,g:
ri
gh d.
All Grades of Toxicity (>1%)—Injection site pain, hot flushes, pain,
t
© ep
leg pain, fatigue, HTN, headache, vomiting, skeletal pain, insomnia,
2 0 ro
impotence, emotional lability, anemia, pruritus, urinary retention, UTI
08 du
No Boxed Warning
M tio
cM n
ah in
c
on w
Pu ol
bl e o
is
h
hi
ng n p
r
G art
i
ro
up wit
un ho
le ut
ss
ot rm
he
pe
rw sio
is
is
e
no s p
n
t e ro h
i
d. ib
tei
d.

Vinblastine Vincristine
Various; powder for injection 10-mg vial solution; solution for Vincasar PFS (Teva Pharmaceuticals), various; solution for
injection 1 mg/mL in 10- and 25-mg vials injection 1 mg/1 mL in 1-, 2-, 5-mg vials
Indications: Palliative treatment of generalized Hodgkin’s disease; Indications: Monotherapy for acute leukemia; in combination
lymphocytic lymphoma; histiocytic lymphoma; advanced myco- for Hodgkin’s disease, NHL, neuroblastoma, Wilms’ tumor,
sis fungoides; advanced testicular carcinoma; Kaposi’s sarcoma; rhabdomyosarcoma
Letterer-Siwe disease; choriocarcinoma resistant to other chemo- Mode & Vehicle of Administrationa,b: Peripheral: I.V. push over
therapy; breast carcinoma unresponsive to endocrine surgery/hor- 1 minute.
monal therapy
Central line: I.V. push over 1 minute. May give slow I.V. push or as
A
Mode & Vehicle of Administrationa,b: Peripheral: I.V. push over
ll
dilute I.V. infusion.
ri
1 minute.
gh
Co es
Usual Single-Agent Dose Rangec-e: 1- to 2-mg/m2 single dose
ts
py erv
Central line: I.V. push over 1 minute. May give slow I.V. push or as weekly; total single doses of 1.4 mg seldom exceeded in adults.
ri
dilute I.V. infusion. Usual pediatric dose is 2 mg/m2. In children ≤10 kg or 1 m2, give
gh d.
Usual Single-Agent Dose Rangec-e: Adult: first dose, 3.7 mg/m2; 0.05 mg/kg weekly.
t
© ep
e
second dose, 5.5 mg/m2; third dose, 7.4 mg/m2; fourth dose, 9.25 Special Precautions/Instructions: Overwrap of syringe must be
2 0 ro
mg/m2; fifth dose, 11.1 mg/m2. Pediatric: 6.5 mg/m2 for Letterer-
R
labeled: “Do not remove covering until moment of injection. Fatal
08 du
Siwe disease, 6 mg/m2 for Hodgkin’s disease, 3 mg/m2 for testicu- if given intrathecally. For I.V. use only.” Reduce dose by 50% in
M tio
lar germ cell carcinomas. patients with bilirubin ≥3 mg/dL. Pregnancy category D.
cM n
Special Precautions/Instructions: Do not exceed 18.5 mg/m2/
ah in
c
Toxicitiesf,g:
dose in adults. Reduce dose by 50% for patients with bilirubin ≥3
on w
mg/dL. In the event of extravasation, heat may be applied to the All Grades of Toxicity—Anaphylaxis, rash, edema, constipation,
Pu ol
site. Pregnancy category D. abdominal cramps, weight loss, nausea, vomiting, oral ulceration,
bl e o
diarrhea, paralytic ileus, intestinal necrosis and/or perforation,
is
h
Toxicitiesf,g:
hi
anorexia, polyuria, dysuria, urinary retention, HTN, hypotension,
ng n p
All Grades of Toxicity—Leukopenia, anemia, thrombocytopenia, sensory impairment, paresthesia, neuritic pain, motor difficulties,
G art
alopecia, light sensitivity, constipation, anorexia, nausea, vomiting, loss of deep tendon reflexes, foot drop, ataxia, paralysis, cranial
ro
up wit
abdominal pain, ileus, vesiculation of the mouth, pharyngitis, diar- nerve manifestations, paresis, jaw pain, pharyngeal pain, parotid
rhea, hemorrhagic enterocolitis, bleeding from an old peptic ulcer, gland pain, bone pain, back pain, limb pain, myalgias, convulsions,
un ho
rectal bleeding, paresthesias, loss of deep tendon reflexes, periph- coma, transient cortical blindness, optic atrophy, SOB, broncho-
le ut
ss
eral neuritis, mental depression, headache, convulsions, HTN, MI, spasm, dyspnea, SIADH, anemia, leukopenia, thrombocytopenia,
ot rm
angina pectoris, CVA, Raynaud’s phenomenon, malaise, bone pain, alopecia, rash, fever, headache
he
weakness, pain in tumor-containing tissue, dizziness, jaw pain,
pe
Boxed Warning—Leakage into surrounding tissue during I.V.
rw sio
skin vesiculation, SIADH, SOB, bronchospasm, dyspnea administration may cause considerable irritation. Fatal if given IT.
is
is
e
Boxed Warning—Leakage into surrounding tissue during I.V. If extravasation occurs, the injection should be discontinued imme-
no s p
administration may cause considerable irritation. Fatal if given IT. diately.
t e ro h
If extravasation occurs, the injection should be discontinued imme-
d.
Comments—In general, the incidence of AEs appears to be
diately. dose-related.
Comments—In general, the incidence of AEs appears to be dose-
ib
related. With the exception of epilation, leukopenia, and neuro-
tei
logic side effects, AEs generally have not persisted for longer than Handle as Hazardous Drugh: Yes1-5
d.
24 hours.

Vinorelbine
Navelbine (Fabre Pharmaceuticals Inc), Teva Pharmaceuticals,
Table 2. Treatments for Extravasation of
various; 10-, 50-mg vials Specific Chemotherapeutic Agents
Indications: As a single agent or in combination with cisplatin Thermal Antidote/

for first-line treatment of ambulatory patients with unresectable, Agent Treatment Dispersion Agent
advanced NSCLC
Alkylating No consistent Sodium thiosulfate:
Mode & Vehicle of Administrationa,b: Infuse diluted drug I.V. over
agents recommenda- Prepare 1/6 molar
6-10 minutes into a free-flowing I.V. line or directly into a central
line. Flush the vein with at least 75 to 125 mL NS or D5W adminis- Cisplatin tions; hot or cold (0.17 mol/L) solution.
A
tered over 10 minutes or more. Mechlor- compresses not Inject 2 mL for every
ll
ri
ethamine proven effective 1 mg mechlorethamine
Usual Single-Agent Dose Rangec-e: Single agent: 30 mg/m2
gh
Co es
weekly. With cisplatin: 25 mg/m2 weekly. Dosage adjustments or 100 mg cisplatin
ts
py erv
extravasated.
ri
should be made for hematologic toxicity (based on granulocyte
gh d.
count) or hepatic insufficiency (based on total bilirubin).
t
© ep
Anthracyclines Cold compresses DMSO: Apply 1-2 mL
e
Special Precautions/Instructions: Do not administer to patients
2 0 ro
with pretreatment granulocyte counts <1,000/mm3. Pregnancy Doxorubicin for 15-20 min of 99% DMSO topi-
08 du
category D. Daunorubicin 4 times daily cally every 4-6 h ×
M tio
Toxicitiesf,g: Epirubicin × 1-2 d 3-14 d. Allow to
cM n
Idarubicin air dry. Or: dexraz-
ah in
c
Grade 3 or 4 Toxicity—Asthenia, elevated AST, elevated
oxane (Totect,
on w
bilirubin, constipation, injection site reactions, injection site pain,
TopoTarget) 1,000
Pu ol
nausea, vomiting, dyspnea, diarrhea, peripheral neuropathy,
bl e o
alopecia, granulocytopenia, leukopenia, anemia, thrombocyto- mg/m2 I.V. over 1-2 h
is
h
on day 1 (within 6 h
hi
penia, phlebitis
ng n p
Boxed Warning—Severe granulocytopenia, resulting in increased of extravasation)
G art
susceptibility to infection, may occur; local tissue necrosis and/or and day 2, then 500
ro
mg/m2 I.V. on day 3.
up wit
thrombophlebitis if extravasation occurs during administration.
un ho
le ut
Epipodo- Warm pack Hyaluronidase: Inject
ss
phyllotoxins immediately for 150-900 units through
ot rm
Etoposide 30-60 min, then existing I.V. line or
he
pe
rw sio
Teniposide alternate off/on subcutaneously; may
is
every 15 min × 1 d be repeated in 3-4 h.
is
e
no s p
n
Mitomycin-C Cold compresses DMSO: Apply 1-2 mL
t e ro h
i
d.
for 15-20 min of 99% DMSO topically
4 times daily × every 4-6 h × 3-14 d.
ib
1-2 d Allow to air dry.
tei
d.
DMSO, dimethyl sulfoxide
continued

References
Table 2. Treatments for Extravasation of 1. University of Michigan Hospitals and Health Centers. Chemotherapy guidelines
(revised February 2003). Ann Arbor, MI: University of Michigan Hospitals and
Specific Chemotherapeutic Agents continued Health Centers.
2. Pharmaceutical Research and Manufacturers of America (PhRMA) based on infor-
Thermal Antidote/ mation from: American Hospital Formulary Service (AHFS) Drug Information (DI)
Agent Treatment Dispersion Agent monographs published by the American Society of Health-System Pharmacists
(ASHP) in selected AHFS pharmacologic–therapeutic classification categories
Taxanes Inconsistent Hyaluronidase: Inject (ASHP/AHFS DI 2003). Physician’s Desk Reference for Drug Interactions. Montvale,
NJ: Thomson Healthcare [www.pdr.net/pdrnet]. Accessed March 9, 2004.
Docetaxel recommendations 150-900 units through
Sweetman SC, ed. Martindale: the Complete Drug Reference. 33rd ed. London, UK:
Paclitaxel for ice packs or existing I.V. line or The Royal Pharmaceutical Society of Great Britain; 2002. Shepard TH. Catalog of
A
warm compresses subcutaneously; may Teratogenic Agents. 10th ed. Baltimore, MD: Johns Hopkins University Press; 2001
ll
[www.depts.washington.edu/~terisweb]. Accessed February 2004. Schardein JL.
ri
be repeated in 3-4 h.
gh
Co es
Chemically Induced Birth Defects. 3rd ed, rev. New York, NY: Marcel Dekker, Inc;
ts
py erv
2000. REPROTOX. An information system on environmental hazards to human
Vinca alkaloids Warm pack Hyaluronidase: Inject
ri
reproduction and development. Washington, DC: Columbia Hospital for Women
gh d.
Vinblastine immediately for 150-900 units through Medical Center, Reproductive Toxicology Center; 2003 [http://reprotox.org].
t
Accessed February 2004.
© ep
Vincristine 30-60 min, then existing I.V. line or
2 0 ro
Vindesine alternate off/on subcutaneously; may 3. National Institutes of Health Clinical Center. Hazard communication program
08 du
(revised August 2002). Bethesda, MD: National Institutes of Health Clinical
(Eldisine, Lilly; every 15 min × 1 d be repeated in 3-4 h. Center.
M tio
seeking
cM n
4. Northside Hospital. Hazardous drug safe handling policy (revised August 2002).
approval)
ah in
c
Atlanta, GA: Northside Hospital.
Vinorelbine
on w
5. The Johns Hopkins Hospital. Chemotherapy guidelines (revised September
Pu ol
2002). Baltimore, MD: The Johns Hopkins Hospital.
bl e o
DMSO, dimethyl sulfoxide
is
h
hi
Suggested Readings
ng n p
Abrahm JL, Pellerin LM. Indwelling access devices. In: Hoffman R, Benz EJ Jr, Shattil
G art
i
SJ, et al, eds. Hematology: Basic Principles and Practice. 4th ed. Orlando, FL: Churchill
ro
up wit
Livingstone; 2005.
un ho
Dorr RT. Pharmacologic management of vesicant chemotherapy extravasation. In: Dorr
RT, Von Hoff DD, eds. Cancer Chemotherapy Handbook. 2nd ed. Norwalk, CT: Appleton
le ut
ss
& Lange; 1994.
ot rm
Drug consults: cytotoxic drug extravasation therapy. Greenwood Village, CO:
he
Thomson Micromedex; 2003.
pe
rw sio
Ener RA, Meglathery SB, Styler M. Review: extravasation of systemic hemato-onco-
is
is
e
logical therapies. Ann Oncol. 2004;15:858-862.
no s p
Introduction to chemotherapy drugs: extravasation. In: Wilkes GM, Barton-Burke
t e ro h
M, eds. 2005 Oncology Nursing Drug Handbook. Boston, MA: Jones and Barlett
d.
Publishers; 2005.
Langstein HN, Duman H, Seeling D, Butler CE, Evans GRD. Retrospective study
ib
of the management of chemotherapeutic extravasation injury. Ann Plast Surg.
ite
2002;49:369-374.
d.
Preparation, administration, and disposal of chemotherapeutic agents. In: Cleri LB,
Haywood R, eds. Oncology: Pocket Guide to Chemotherapy. 5th ed. Philadelphia, PA:
Mosby; 2002.
Schrijvers DL. Extravasation: a dreaded complication of chemotherapy. Ann Oncol.
2003;14(suppl 3):26-30.

3 consecutive head nurses on an oncology unit who worked

Safe Handling with chemotherapy for several years.4
Of Hazardous Drugs Reproductive risks: Several adverse outcomes have been
associated with occupational exposure to HDs. Fetal loss,
Martha Polovich, MN, RN, AOCN miscarriage, or spontaneous abortions5-7; fetal abnormali-
Associate Director of Clinical Practice
ties8; infertility9-11; and preterm births and learning disabili-
Duke Oncology Network ties in offspring9 have all been reported.
Durham, North Carolina Cancer risk: Skov et al reported an increase in cases of
Luci A. Power, MS, RPh leukemia in nurses.12 Another study found an increased risk
A
Senior Consultant for both non-Hodgkin’s lymphoma and skin cancer in phar-
ll
macy technicians.13
ri
Power Enterprises
gh
Co es
San Francisco, California
ts
py erv
Routes of Exposure
ri
gh d.
H
azardous drugs (HDs) pose a potential health risk to Exposure refers to actual contact with a hazardous sub-
t
© ep
e
health care workers who are exposed during com- stance. Just working with HDs does not imply that work-
2 0 ro
R
pounding, administration, spill control, and waste- ers are exposed; however, there are many opportunities for
08 du
M tio
handling activities. Such drugs require special handling exposure by several routes.
cM n
because of their inherent toxicities. Because anticancer Inhalation: Air contaminated by aerosolized drugs can be
ah in
c
drugs make up the bulk of those agents classified as HDs, inhaled during activities that generate drug aerosols, such
on w
pharmacists and other health care professionals working as transferring drugs from one container to another during
Pu ol
bl e o
with oncology patients must be well versed in the safe han- drug compounding, spiking or unspiking I.V. bags or bottles,
is
h
hi
dling procedures that the Occupational Safety and Health and cleaning up spills.
ng n p
Administration (OSHA) considers crucial to health care Skin absorption: Direct contact can occur when workers
G art
i
worker safety.1
ro
handle drugs with unprotected hands or when an HD leaks
up wit
Any agent that possesses one or more of the following or spills. Indirect contact can occur from surfaces that have
un ho
characteristics is considered an HD2: been unintentionally contaminated with HDs during drug
le ut
ss
• carcinogenicity compounding and administration or because of incom-
ot rm
• teratogenicity or developmental toxicity plete decontamination after spills.14,15 Several authors also
he
pe
• reproductive toxicity found measurable concentrations of HDs on the exteriors
rw sio
is
• organ toxicity at low doses of drug vials.16,17
is
e
no s p
• genotoxicity Ingestion: Ingestion of contaminated food or drink or
t e ro h
• structure or toxicity similar to that of drugs classified as other hand-to-mouth contact can result in drug exposure.
d.
hazardous according to the preceding criteria.2 Accidental injection: Injury with needles or other contami-
Some of the risks of occupational exposure to HDs are nated sharps, such as broken glass vials, is another route of
ib
i
the following: exposure.
te
d.
Acute symptoms: These include dizziness, headache, hair
loss, abdominal pain, nasal sores, contact dermatitis, allergic Recommendations for Safe Handling
reactions, tissue injury, and eye injury from contact.3 Current recommendations for the safe handling of
Organ damage: Whether long-term occupational HDs come from OSHA, 1 the National Institute for
exposure to cytotoxic drugs is associated with organ dam- Occupational Safety and Health (NIOSH),2 the Oncology
age is controversial; however, liver damage was reported in Nursing Society (ONS),18 and the American Society of

Health-System Pharmacists (ASHP).19 All of these organiza- performance to reduce exposure.

tions describe similar methods of limiting worker exposure, Personal protective equipment—Garments that have been
including environmental controls, primary engineering con- designed to protect workers from exposure during drug
trols (PECs), work practice controls, and personal protec- handling, including the following:
tive equipment (PPE). • Double gloves that have been tested to the 2005
In 2007, the United States Pharmacopeial Convention American Society for Testing and Materials (ASTM)
released a revision of the 2004 US Pharmacopeia (USP) standard for resistance of permeation to chemo-
Chapter <797> Pharmaceutical Compounding—Sterile therapy drugs.24 Double sterile gloves are required for
Preparations, which became effective in 2008.20,21 This revi- compounding.21
A
sion includes a section specific to HD compounding and • Tested gloves that are powder-free and are made
ll
ri
elevates much of the 2004 NIOSH Alert to enforceable of latex, nitrile, or polychloroprene (Neoprene).
gh
Co es
mandates. In addition, USP Chapter <797> is applicable to Recommended glove-wearing time is 30 minutes.
ts
py erv
r
ri
all settings where sterile doses of HDs are compounded, • Gowns that have been tested with HDs, are disposable
gh d.
not just hospitals and clinics. USP Chapter <797> com- and intended for single use, and have cuffs and back
t
© ep
e
pounding requirements include environmental and primary closure. Coated gowns are the most protective.25,26
2 0 ro
R
engineering controls to ensure both a sterile product and • Eye and face protection when splashing is possible.
08 du
M tio
appropriate containment of any HD contamination. • Respirator masks for aerosols and spill cleanup.
cM n
Environmental controls—Segregated storage and com-
ah in
c
pounding areas; contained areas with appropriate air chang- Drug Compounding
on w
es per hour; optimal outside exhaust resulting in negative All aseptic compounding of sterile preparations must be
Pu ol
bl e o
pressure storage and buffer and ante areas. These create an done by staff trained and competent in compounding sterile
is
h
HD preparations.2,18,19,21 ChemoChekTM and ChemoTEQTM are
hi
environment to reduce the transfer of contamination.
ng n p
Primary engineering controls—Equipment designed to kits that provide an objective method of validating compe-
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provide an aseptic environment for compounding sterile tency when compounding. Either kit may be used to “cer-
up wit
doses and to contain HD aerosols, such as a biological safety tify” an employee initially and yearly. The process uses a
un ho
cabinet (BSC) or compounding aseptic containment isolator senior trainer to observe actual performance. Sterile com-
le ut
ss
(CACI).20-22 pounding must be performed in an environment that meets
ot rm
Administrative controls—Policies, procedures, scheduling USP Chapter <797> requirements.20 In its 2008 revision,
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pe
practices, and other controls that limit the number of work- USP Chapter <797> specifically addresses HD compound-
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ers who are potentially exposed. ing, including PECs and aseptic work practices.21
is
e
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Medical surveillance programs—A method of identifying General recommendations for drug compounding include
t e ro h
potentially exposed workers by establishing a baseline of the following:
d.
workers’ health, then monitoring their health as it relates • Compound all HDs in a PEC that will contain contami-
to their potential exposure to HDs.23 USP Chapter <797> nated airflow and drug aerosols, as well as provide
ib
i
requires that all compounding personnel of reproductive an International Standards Organization (ISO) 5 high-
te
d.
capability confirm in writing that they understand the risks efficiency particulate air (HEPA)–filtered laminar flow
of handling HDs. Although USP Chapter <797> mandates environment. The PEC is exhausted to the outside
this only for personnel responsible for compounding, pru- atmosphere (preferred) or to the workroom through
dent practice dicates that this requirement should extend a HEPA filter. USP Chapter <797> specifies a Class II
to all personnel who handle HDs.21 BSC and a CACI as possible PECs. A Class II BSC has
Work practice controls—Altering methods of work an open front; a CACI is a closed ventilated cabinet

with fixed-glove assembly. CACIs used to prepare device that mechanically prevents the transfer of environ-
HDs should meet the requirements of USP Chapter mental contaminants into the system and the escape of HD
<797>. or vapor concentrations outside the system.2 Several stud-
• Designate a compounding area that is limited to autho- ies have demonstrated a reduction in surface contamination
rized personnel. Traffic in the compounding area should after the use of a closed system device.27-32 Several devices
be minimized to avoid distractions and to reduce (PhaSeal®, Carmel Pharma; OnGuardTM with TevadaptorTM
transfer of any contamination generated during the components, B Braun; Smart SiteTM and TexiumTM, Cardinal
compounding process to other staff or surfaces. The Health; SpirosTM and GenieTM, ICU Medical) are approved by
HD compounding area should meet the requirements the FDA. To date, only PhaSeal has been studied as effec-
tive in clinical use.27-32 These systems are not a substitute
A
of USP Chapter <797> regarding the segregation of
ll
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HD storage and compounding, the air quality in the for ventilation controls and should be used only within an
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ante room and buffer area, the air changes per hour, appropriate PEC.
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and outside exhaust.
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• Wear tested, sterile, double gloves and a coated gown. Drug Administration
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• Use procedures, such as negative-pressure technique, The precautions outlined by OSHA,1 NIOSH,2 ONS,18 and
2 0 ro
ASHP,19 when followed, can reduce exposure. Recom-
R
that reduce the risk for generating aerosols and drug
08 du
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leakage. mendations for administering drugs are applicable to all
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• Use work practices and decontamination procedures practice settings and include the following:
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that prevent the transfer of contamination from the • Follow universal/standard precautions.
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interior of the cabinet to final product containers and • Perform all drug manipulation activities below eye level.
Pu ol
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the environment. • Wear PPE when retrieving HDs from the delivery
is
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• Use syringes and I.V. sets with Luer lock fittings for HDs. containers.
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Select a syringe large enough so that the syringe is not • Wear appropriate gown and gloves for all drug admin-
G art
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more than 75% full when it contains the entire dose. This istration activities.
up wit
will prevent the plunger from dislodging during use or • Wear a face shield whenever there is a risk for splashing.
un ho
transport. • Use administration sets, needles, and syringes with Luer
le ut
ss
• Keep a small, covered sharps container in the BSC or lock connections.
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CACI. It should be small enough not to interfere with • Use needle-less systems whenever possible.
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the flow characteristics of the PEC. • Avoid expelling air from syringes to reduce the risk for
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• Place final compounded drugs into a sealable bag or other generating aerosols.
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container for transport to the drug administration area. • Place a disposable, plastic-backed absorbent liner
t e ro h
• Place contaminated material (including gloves, under I.V. connection sites.
d.
gowns, and paper liners, if used) immediately into an • Consider gowns and gloves contaminted after handling
HD-labeled, sealable plastic bag.18,19 Seal and discard HDs. Remove them carefully to avoid transfer of con-
ib
i
the bag in an appropriate container for disposal. tamination to clothing or skin.
te
d.
• Wear PPE while decontaminating all reusable equipment
Closed-System Drug Delivery used in drug administration, remove PPE carefully, and
Closed-system transfer devices were developed in the wash hands thoroughly.
past decade to reduce exposure during chemotherapy • Seal used PPE, I.V. tubing, bags, syringes, etc, in a plastic
compounding and administration. NIOSH defines a closed bag and then discard in a container designated for HD
system drug-transfer device (CSTD) as a drug transfer waste.

Table. Supplies and PPE Required Table. Supplies and PPE Required
For Administering Hazardous Drugs For Administering Hazardous Drugs
Routes of Routes of
Administration PPE and Supplies Required Administration PPE and Supplies Required
I.V. push Gown and gloves Intracavitary Gown and gloves

4x4 gauze for use around the Face shield, mask, or safety
injection port goggles as needed for splashing
A
Alcohol swabs Disposable, plastic-backed
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Disposable, plastic-backed absorbent liner
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absorbent liner 4x4 gauze for use around the
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Sealable plastic bag injection port
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Puncture-resistant sharps container Sealable plastic bag
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for needles and breakable items Appropriate hazardous drug
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disposal container
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I.V. infusion Gown and gloves
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Aerosolized Gown and gloves
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Face shield, mask, or safety goggles
Face shield, NIOSH-approved
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as needed for splashing
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4x4 gauze for use around the respirator, mask, and/or safety
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injection port goggles
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Alcohol swabs Sealable plastic bag
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Disposable, plastic-backed Appropriate hazardous drug
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absorbent liner disposal container
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Sealable plastic bag
up wit
Puncture-resistant sharps container NIOSH, National Institute of Occupational Safety and Health;
PPE, personal protective equipment
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for needles and breakable items
le ut
Reprinted with permission from Oncology Nursing Society. Polovich M, ed.
ss
Safe Handling of Hazardous Drugs. Pittsburgh, PA: Oncology Nursing Press;
Intramuscular or Gown and gloves
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2003:25. Copyright © 2003, Oncology Nursing Press.
he
subcutaneous Alcohol swabs
pe
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injection Sealable plastic bag
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Puncture-resistant sharps container
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for needles and breakable items
t e ro h
The Table lists supplies and PPE required for administer-
d.
Oral or topical Gown and gloves ing HDs by specific routes.
Face shield, mask, or safety goggles
ib
as needed for splashing Formulations, Packaging, and Transport
i
te
Disposable, plastic-backed
d.
Changes in formulations and packaging may reduce the
absorbent liner
Sealable plastic bag
potential for exposure of health care workers to HDs.
Appropriate hazardous drug • Avoid ampules whenever possible to reduce the han-
disposal container dling of sharps and spilling of drugs during disposal.
• Choose injectable liquid formulations over powder
whenever available to reduce the number of necessary

manipulations. protected and trained personnel.1 Identify the area with a

• Select nonreactive plastic polymer vials or shrouded or warning sign to limit access to the area. Clean up the spill
coated vials to reduce exposure from breakage. while wearing the following PPE:
• In high-volume pharmacies, use multiple-dose vials with • 2 pairs of chemotherapy-designated gloves
a CSTD. • utility gloves and/or scoop for sharps (eg, broken glass)
• For solid oral formulations, choose drugs provided by
• chemotherapy-designated gown
the manufacturer in unit-dose packaging.
• Select solid oral formulations that are either coated tab- • respiratory protection
lets or capsules, or tablets with “core drug” to reduce the • disposable shoe coverings.
A
risk for release of HD powder from drug containers. All HD spills should be reported to the appropriate safety
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• Oral formulations of HDs should not be handled by a department personnel.
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robotic counter.
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Acute Exposure
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Drug Disposal For acute exposure, such as after a spill on skin or mucous
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Safety measures such as the following must be taken membranes, the employee should initiate the following
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R
during the handling and disposal of hazardous waste steps immediately:
08 du
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products: Skin exposure—Remove contaminated clothing and/or
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• Use thick, leak-proof plastic waste bags of a specific, PPE; wash affected area thoroughly with soap and water1
ah in
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identifiable color to contain discarded gloves, gowns, and consult the material safety data sheet (MSDS) for drug-
on w
and any other disposable material contaminated by specific instructions.
Pu ol
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HDs. Eye exposure—Flush eye(s) with water or isotonic eye
is
h
wash for 15 minutes1; report to an emergency department
hi
• Do not clip or recap needles, and do not crush syringes
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that have been used to deliver HDs. and consult the MSDS for drug-specific instructions.
G art
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• Place contaminated waste materials in sealed plastic Inhalation or ingestion—Report to the employee health
up wit
bags and discard them inside covered waste containers professional or emergency department, based on symp-
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clearly labeled as containing hazardous materials. toms, and consult the MSDS for drug-specific instructions.
le ut
ss
• Have at least one such receptacle available in every Follow-up for acute exposure should include the
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area where HDs are handled. following:
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• OSHA-trained staff, who are knowledgeable about • reporting to the employee health professional
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is
the Hazardous Operations and Emergency Response • completing a report of employee injury or exposure
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no s p
(HAZWOPER) standard,33 should transport waste to • following the organizational policy related to reporting
t e ro h
storage areas to await disposal. requirements for workers’ compensation.
d.
• Handle HD-related waste separately from other
trash and dispose of it in accordance with applicable Conclusion
ib
i
Environmental Protection Agency, state, and local Adopting such measures as the use of PPE, PECs, safer
te
d.
regulations. work practices, medical surveillance, and new systems for
safely compounding and administering HDs can help mini-
Spill Management mize the risk for exposure of health care workers involved
According to the OSHA guidelines, incidental spills and in compounding, administration, spill control, and waste-
breakage should be cleaned up immediately by properly handling activities.

References 18. Polovich M, White J, Kelleher LO. Chemotherapy and Biotherapy Guidelines and
Recommendations for Practice. 2nd ed. Pittsburgh, PA: Oncology Nursing Press;
1. Occupational Safety and Health Administration. OSHA technical manual, TED 1-0.15A
2005:240.
Sec VI, Chapter 2: Controlling Occupational Exposure to Hazardous Drugs; 1999.
http://www.osha.gov/dts/osta/om/otm_vi_2.html. Accessed August 28, 2008. 19. American Society of Health System Pharmacists. ASHP guidelines on handling
HDs. Am J Health Syst Pharm. 2006;63:1172-1193.
2. National Institute for Occupational Safety and Health. Preventing occupational
exposure to antineoplastic and other HDs in health care settings. Washington, 20. United States Pharmacopeial Convention, Inc. Chapter <797> Pharmaceutical
DC: National Institute for Occupational Safety and Health; 2004. http://www.cdc. Compounding—Sterile Preparations. United States Pharmacopeia. 28th ed.
gov/niosh/docs/2004-165/. Accessed August 28, 2008. Rockville, MD: United States Pharmacopeial Convention, Inc; 2005:2461-2477.
3. Harrison BR. Risks of handling cytotoxic drugs. In: Perry MC, ed. The Chemotherapy 21. United States Pharmacopeial Convention, Inc. Chapter <797> Pharmaceutical
Source Book. Philadelphia, PA: Lippincott Williams & Wilkins; 2001:566-582. Compounding—Sterile Preparations. United States Pharmacopeia. 31st ed.
4. Sotaniemi EA, Sutinen S, Arranto, et al. Liver damage in nurses handling cyto- National Formulary, 26th rev. Rockville, MD: United States Pharmacopeial
A
static agents. Acta Med Scand. 1983;214:181-189. Convention, Inc. Official from May 1, 2008.
ll
22. Controlled Environment Testing Association. Applications guide for the use
ri
5. Selevan SG, Lindbohm ML, Hornung RW, Hemminki K. A study of occupa-
gh
Co es
tional exposure to antineoplastic drugs and fetal loss in nurses. N Engl J Med. of compounding isolators in compounding sterile preparations is health-
ts
py erv
1985;313:1173-1178. care facilities. CAG-001-2005. http://www.cetainternational.org/reference/
ri
ApplicationsGuideBarrierIsolator110805.pdf. Accessed August 28, 2008.
gh d.
6. Stucker I, Caillard JF, Collin R, Gout M, Poyen D, Hemon D. Risk of spontaneous
abortion among nurses handling antineoplastic drugs. Scand J Work Environ Health. 23. National Institute for Occupational Safety and Health. Workplace solutions:
t
© ep
medical surveillance for healthcare workers exposed to HDs. NIOSH Publication
e
1990;16:102-107.
2 0 ro
No. 2007-117. http://www.cdc.gov/niosh/docs/wp-solutions/2007-117/. Accessed
7. Valanis BG, Vollmer WM, Steele P. Occupational exposure to antineoplastic
08 du
August 28, 2008.
agents: self-reported miscarriages and stillbirths among nurses and pharmacists.
M tio
J Occup Environ Med. 1999;41:632-638. 24. American Society for Testing and Materials. D 6978-05 Standard Practice for
cM n
Assessment of Resistance of Medical Gloves to Permeation by Chemotherapy
8. Hemminki K, Kyyronen P, Lindbohm ML. Spontaneous abortions and malforma-
Drugs. West Conshohocken, PA: ASTM; 2005.
ah in
c
tions in the offspring of nurses exposed to anaesthetic gases, cytotoxic drugs, and
on w
other potential hazards in hospitals, based on registered information of outcome. J 25. Connor TH. An evaluation of the permeability of disposable polypropylene-
based protective gowns to a battery of cancer chemotherapy drugs. Appl Occup
Pu ol
Epidemiol Community Health. 1985;39:141-147.
Environ Hyg. 1993;8:785-789.
bl e o
9. Martin S. Chemotherapy handling and effects among nurses and their offspring.
is
h
Oncol Nurs Forum. 2005;32:425. Abstract. 26. Harrison BR, Kloos MD. Penetration and splash protection of six disposable gown
hi
materials against fifteen antineoplastic dugs. J Oncol Pharm Pract. 1999;5:61-66.
ng n p
10. Valanis BG, Vollmer W, Labuhn K, Glass A. Occupational exposure to antine-
oplastic agents and self-reported infertility among nurses and pharmacists. J 27. Sessink PJ, Rolf ME, Ryden NS. Evaluation of the PhaSeal® HD containment sys-
G art
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ro
Occup Environ Med. 1997;39:574-580. tem. Hosp Pharm. 1999;34:1311-1317.
up wit
11. Fransman W, Roeleveld N, Peelen S, de Kort W, Kromhout H, Heederik D. 28. Connor TH, Anderson RW, Sessink PJ, Spivey SM. Effectiveness of a closed-
un ho
Nurses with dermal exposure to antineoplastic drugs: reproductive outcomes. system device in containing surface contamination with cyclophosphamide and
ifosfamide in an I.V. admixture area. Am J Health Syst Pharm. 2002;59:68-72.
le ut
Epidemiology. 2007;18:112-119.
ss
12. Skov T, Lynge E, Maarup B, Olsen J, Rorth M, Winthereik H. Risks for physicians 29. Vandenbroucke J, Robays H. How to protect environment and employees against
ot rm
handling antineoplastic drugs. Lancet. 1990;336:1446. cytotoxic agents: the UZ Ghent experience. J Oncol Pharm Pract. 2001;6:146-152.
he
pe
13. Hansen J, Olsen JH. Cancer morbidity among Danish female pharmacy techni- 30. Nygren O, Gustavsson B, Strom L, Eriksson R, Jarneborn L, Friberg A. Exposure to
rw sio
cians. Scand J Work Environ Health. 1994;20:22-26. anti-cancer drugs during preparation and administration: investigations of an open
is
is
e
14. McDevitt JJ, Lees PS, McDiarmid MA. Exposure of hospital pharmacists and and closed system. J Environ Monit. 2002;4:739-742.
no s p
nurses to antineoplastic agents. J Occup Med. 1993;35:56-60. 31. Wick C, Slawson MH, Jorgenson JA, Tyler LS. Using a closed-system protective
t e ro h
15. Connor TH, Anderson RW, Sessink PJ, Broadfield L, Power LA. Surface contami- device to reduce personnel exposure to antineoplastic agents. Am J Health Syst
d.
nation with antineoplastic agents in six cancer treatment centers in Canada and Pharm. 2003;22:2314-2320.
the United States. Am J Health Syst Pharm. 1999;56:1427-1432. 32. Harrison BR, Peters BG, Bing MR. Comparison of surface contamination with
ib
16. Sessink PJ, Boer KA, Scheefhals AP, Anzion RB, Bos RP. Occupational exposure cyclophosphamide and fluorouracil using a closed-system drug transfer
i
device versus standard preparation techniques. Am J Health Syst Pharm.
te
to antineoplastic agents at several departments in a hospital. Environmental
d.
contamination and excretion of cyclophosphamide and ifosfamide in urine of 2006;63:1736-1744.
exposed workers. Int Arch Occup Environ Health. 1992;64:105-112. 33. US Department of Labor, Occupational Safety and Health Administration.
17. Connor TH, Sessink PJ, Harrison BR, et al. Surface contamination of chemo- Hazardous waste operations and emergency response. 29 CFR 1910.120. http://
therapy drug vials and evaluation of new vial cleaning techniques: results of three www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=STANDARDS&p_
studies. Am J Health Syst Pharm. 2005;62:475-484. id=9765. Accessed August 28, 2008.

Chemotherapy-Induced Table 1. Prevention of Nausea and Vomiting

Nausea and Vomiting:
Anticipatory
Treatment Guidelines Preferred therapy is the use of psychological techniques.
Benzodiazepines can be used in addition or as an
David G. Frame, PharmD William Leslie, MD alternative.
Clinical Assistant Professor of Pharmacy Assistant Professor of Medicine
College of Pharmacy Rush Medical College Acute-onset
University of Michigan Rush University
A
Highly emetogenic chemotherapy
ll
Clinical Pharmacist Chicago, Illinois
ri
University of Michigan Hospital Preferred therapy is a 3-drug antiemetic regimen that
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Ann Arbor, Michigan includes a single dose of a 5-HT3–receptor antagonist,
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dexamethasone, and aprepitant (or fosaprepitant).
gh d.
F
our groups—the American Society of Clinical Oncology Moderately emetogenic chemotherapy
t
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(ASCO),1 the European Society for Medical Oncology Preferred therapy is a 5-HT3–receptor antagonist plus
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(ESMO),2 the Multinational Association of Supportive dexamethasone.
08 du
Mildly emetogenic chemotherapy
Care in Cancer (MASCC),3 and the National Comprehensive
M tio
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Preferred therapy is a low dose of a single agent such as a
Cancer Network (NCCN)4—have all published updated anti-
ah in
c
corticosteroid or a dopamine antagonist.
emetic guidelines with very similar recommendations.
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Minimally emetogenic chemotherapy
This review summarizes the updated recommendations
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Antiemetic agents should not be routinely used in patients
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of the MASCC to help physicians, nurses, and pharmacists without a history of nausea and vomiting.
is
h
hi
select the most appropriate antiemetic regimens for indi-
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viduals receiving chemotherapy; it includes Tables and a Delayed-onset
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Figure providing a useful algorithm of the recommended Highly emetogenic chemotherapy
up wit
course of antiemetic care.3 The combination of dexamethasone and aprepitant is
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recommended for cisplatin-containing regimens and dex-
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Prevention of Nausea and Vomiting amethasone alone for non–cisplatin-containing regimens.
ss
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Table 1 lists recommendations for the prevention of vari- Moderately emetogenic chemotherapy
he
Preferred therapy is oral dexamethasone with chemotherapy
pe
ous types of chemotherapy-induced nausea and vomit-
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agents known to cause significant delayed nausea and
is
ing (CINV).3 Tables 2 and 3 list dosing information for
is
e
vomiting. A 5-HT3–receptor antagonist can be used as an
no s p
the 5-HT 3–receptor antagonists: dolasetron (Anzemet, alternative.
t e ro h
Sanofi-Aventis), granisetron (Kytril, Roche), ondansetron
d.
(Zofran, GlaxoSmithKline), and palonosetron (Aloxi, Eisai/
MGI Pharma). Dosing information is also included for dexa-
ib
i
methasone and aprepitant/fosaprepitant (Emend, Merck). etoposide, ifosfamide, imatinib (Gleevec, Novartis), irino-
te
d.
There are no clinically relevant differences in the effec- tecan, paclitaxel, vinblastine, vincristine, and vinorelbine,
tiveness of the 5-HT3–receptor antagonists for preventing should be coadministered with aprepitant/fosaprepitant
acute nausea and vomiting when they are given as rec- cautiously.5 The dose of dexamethasone should be reduced
ommended. Aprepitant and its prodrug, fosaprepitant, are by 50% when it is administered with aprepitant.5 Clinically
inhibitors of cytochrome P-450 (CYP) 3A4.5 Therefore, other significant changes in the international normalized ratio
chemotherapy agents metabolized by CYP3A4, including (INR) have been documented in patients on warfarin after

Table 2. Recommended Doses of Table 3. Recommended Dosing of

5-HT3–Receptor Antagonists for Acute Emesis Dexamethasone and Aprepitant
Agent Route Dose Dosing and

Dexamethasonea Schedule
Dolasetron I.V. 100 mg or
1.8 mg/kg High risk Acute emesis 20 mg once
Oral 100 mg Delayed emesis 8 mg/d x 3-4 d
A
Granisetron I.V. 1 mg or Moderate risk Acute emesis 8 mg once
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ri
0.01 mg/kg Delayed emesis 8 mg/d x 2-3 db
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Co es
Oral 2 mg (or 1 mga)
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Low risk Acute emesis 4-8 mg once
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Ondansetron I.V. 8 mg or
t
0.15 mg/kg
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Dosing and
e
Oral 16 mgb
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Aprepitant Schedule
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Palonosetron I.V. 0.25 mg
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Acute emesis 125 mg orally
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Oral 0.5 mg once
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a
The 1-mg dose is preferred by some panelists; it has been evaluated in a
small randomized study of moderately emetogenic chemotherapy and in
Delayed emesis 80 mg/d
Pu ol
a Phase II study of highly emetogenic chemotherapy. orally x 2 d
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is
h
b
Randomized studies have tested an 8-mg bid schedule.
hi
a
The dose of dexamethasone should be reduced by 50% when given with
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5-HT3, 5-hydroxytryptamine type 3 (serotonin type 3) aprepitant because of a drug interaction.
G art
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b
ro
Many panelists give the dosage as 4 mg bid.
up wit
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ss
the administration of aprepitant.5 rophenones are effective, but because of the recent warn-
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ing about QT prolongation and potential torsades de pointes
he
Treatment for Breakthrough Nausea and Vomiting
pe
with droperidol, a patient’s electrocardiogram must be evalu-
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is
When the primary antiemetic regimen fails to appropriate- ated before droperidol is used.7 Many studies have shown
is
e
no s p
ly control nausea and vomiting, another agent with a differ- that metoclopramide in standard doses is effective in com-
t e ro h
ent mechanism of action should be added. Phenothiazines, bination, but not as a single agent.8 Thus, the phenothiazines
d.
substituted benzamides, and butyrophenones have anti- are often used as primary agents for second-line therapy.
dopaminergic and anticholinergic properties and are often Also newly approved for use as second-line therapy are
ib
i
effective when a 5-HT3–receptor antagonist has failed. Most the cannabinoids: dronabinol and the newly approved nabi-
te
d.
chemotherapy agents, except for carboplatin and cyclo- lone (Cesamet, Valeant). It is thought that their antiemetic
phosphamide, generally cause an early release of sero- effect is caused by interaction with cannabinoid receptors
tonin, which is why the 5-HT3–receptor antagonists have (CB1). In randomized trials, both cannabinoids were more
the greatest efficacy against acute-onset nausea and vomit- effective than prochlorperazine.9 A meta-analysis also con-
ing.6 Dopaminergic pathways and substance P may be more cluded that the cannabinoids were more effective than
involved in delayed-onset nausea and vomiting. The buty- many conventional antiemetics, including prochlorperazine

Individual Patient Risk Assessment

• History of N/V
• Age
• Anxiety
• History of motion sickness
Single dose
• Gender
of 5-HT3 –
• Hydration status
receptor
antagonist
I.V. or PO + Cisplatin regimen:
A
dexamethasone dexamethasone
ll
Anticipatory 10 mg I.V. + Prophylactic 8 mg daily
ri
gh
post-chemotherapy
Co es
N/V or high aprepitant 125 mg x 3-4 d
ts
antiemetic regimen + aprepitant
py erv
anxiety level PO or fosaprepitant
Highly for chemotherapy
ri
115 mg I.V. 80 mg
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emetogenic associated with PO x 2 d
t
delayed-onset N/V
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• Psychological Single dose
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techniques of 5-HT3 –receptor Dexamethasone
• ± Benzo- Moderately 8 mg daily x
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antagonist I.V. or
emetogenic Prophylactic
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diazepines PO + dexamethasone 2-3 d
pre-chemotherapy
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8 mg I.V.
antiemetic
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regimen
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Mildly for acute-onset
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Chemotherapy N/V Dexamethasone
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h
emetogenic 4-8 mg I.V.
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r
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None recommended Treatment of breakthrough N/V
up wit
Minimally unless patient has
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emetogenic a history of N/V
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Adjunctive therapy: Second-line therapy:
ss
benzodiazepines, use agent of different
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he
cannabinoids class (eg, phenothiazine
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Figure. Treatment algorithm for
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or butyrophenone)
is
chemotherapy-induced nausea and vomiting.
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e
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n
t e ro h
5-HT3, 5-hydroxytryptamine type 3 (serotonin type 3); N/V, nausea and vomiting
d. ib
i
and metoclopramide.10 Adverse effects, particularly related considered, although they have never been proven as effec-
te
d.
to the central nervous system, occurred significantly more tive as single agents. They may be more effective when
often with cannabinoids. In comparison with dronabinol, used as adjunctive anxiolytic agents. Antihistamines also are
nabilone has a longer duration of action, requires less fre- generally ineffective as single agents, but they may provide
quent dosing, and appears not to inhibit CYP enzymes, all value in combination with other antiemetic agents, espe-
of which may make it more convenient to use.11 cially in patients who have a history of motion sickness.12
Adjunctive therapy with benzodiazepines may also be Some patients may also benefit from nonpharmacologic

approaches, such as relaxation techniques, biofeedback, 10. Tramer MR, Carroll D, Campbell FA, et al. Cannabinoids for control of chemo-
therapy induced nausea and vomiting: quantitative systematic review. BMJ.
acupressure, and music therapy. 2001;323(7303):16-21.
11. Ware MA, Daeninck P, Maida V. A review of nabilone in the treatment of chemo-
Conclusion therapy-induced nausea and vomiting. Ther Clin Risk Manag. 2008:4(1):99-107.
The recommendations in the major antiemetic consen- 12. Morrow GR. Susceptibility to motion sickness and the development of anticipa-
sus guidelines are very similar and are represented in this tory nausea and vomiting in cancer patients undergoing chemotherapy. Cancer
Treat Rep. 1984;68(9):1177-1178.
review of the prevention and treatment of CINV. Because of
individual variations in response, neurotransmitter release,
Suggested Readings
and drug metabolism, the efficacy of a certain antiemetic
Chawla SP, Grunberg SM, Gralla RJ, et al. Establishing the dose of the oral NK1 antag-
A
may be decreased, or its toxicity increased. Thus, these
ll
onist aprepitant for the prevention of chemotherapy-induced nausea and vomiting.
ri
guidelines should be considered as general recommenda- Cancer. 2003;97(9):2290-2300.
gh
Co es
tions for the initiation of antiemetic therapy for CINV, but
ts
py erv
Dando TM, Perry CM. Aprepitant: a review of its use in the prevention of chemothera-
ri
treatment should always be individualized, especially when py-induced nausea and vomiting. Drugs. 2004;64(7):777-794.
gh d.
nausea and vomiting have not been completely controlled. De Wit R, Herrstedt J, Rapoport B, et al. Addition of the oral NK1 antagonist aprepi-
t
© ep
tant to standard antiemetics provides protection against nausea and vomiting during
2 0 ro
multiple cycles of cisplatin-based chemotherapy. J Clin Oncol. 2003;21(22):4105-4111.
References
08 du
Eisenberg P, Figueroa-Vadillo J, Zamora R, et al; 99-04 Palonosetron Study Group.
M tio
1. Kris MG, Hesketh PJ, Somerfield MR, et al. American Society of Clinical Improved prevention of moderately emetogenic chemotherapy-induced nausea and
cM n
Oncology guideline for antiemetics in oncology: update 2006. J Clin Oncol. vomiting with palonosetron, a pharmacologically novel 5-HT3 receptor antagonist:
ah in
c
2006;24(18):2932-2947. results of a Phase III, single-dose trial versus dolasetron. Cancer. 2003;98(11):2473-2482.
on w
2. Herrstedt J. Chemotherapy-induced nausea and vomiting: ESMO clinical recom- Grunberg SM. Antiemetic activity of corticosteroids in patients receiving cancer che-
Pu ol
mendations for prophylaxis. Ann Oncol. 2007;18(suppl 2):ii83-ii85. motherapy: dosing, efficacy, and tolerability analysis. Ann Oncol. 2007;18(2):233-240.
bl e o
3. Roila F, Hesketh PJ, Herrstedt J, et al. Prevention of chemotherapy- and radio- Hesketh PJ, Grunberg SM, Gralla RJ, et al. The oral neurokinin-1 antagonist aprepitant
is
h
hi
therapy-induced emesis: results of the 2004 Perugia International Antiemetic for the prevention of chemotherapy-induced nausea and vomiting: a multinational,
ng n p
Consensus Conference. Ann Oncol. 2006;17(1):20-28. Recommendation and slides randomized, double-blind, placebo-controlled trial in patients receiving high-dose cis-
r
updated March 2008: http://www.mascc.org. Accessed August 24, 2008. platin—the Aprepitant Protocol 052 Study Group. J Clin Oncol. 2003;21(22):4112-4119.
G art
i
ro
4. Ettinger DS, Bierman PJ, Bradbury B, et al. Antiemesis. J Natl Compr Canc Netw. Ioannidis JP, Hesketh PJ, Lau J. Contribution of dexamethasone to control of chemo-
up wit
2007;5(1):12-33. therapy-induced nausea and vomiting: a meta-analysis of randomized evidence. J Clin
un ho
Oncol. 2000;18(19):3409-3422.
5. Shadle CR, Lee Y, Majumdar AK, et al. Evaluation of potential inductive effects
le ut
Martin CG, Rubenstein EB, Elting LS, Kim YJ, Osoba D. Measuring chemotherapy-
ss
of aprepitant on cytochrome P450 3A4 and 2C9 activity. J Clin Pharmacol.
2004;44(3):215-223. induced nausea and emesis. Cancer. 2003;98(3):645-655.
ot rm
he
6. Minami M, Endo T, Hirafuji M, et al. Pharmacological aspects of anticancer drug- McCrea JB, Majumdar AK, Goldberg MR, et al. Effects of the neurokinin-1 receptor
pe
rw sio
induced emesis with emphasis on serotonin release and vagal nerve activity. antagonist aprepitant on the pharmacokinetics of dexamethasone and methylpredni-
is
Pharmacol Ther. 2003;99(2):149-165. solone. Clin Pharmacol Ther. 2003;74(1):17-24.
is
e
no s p
7. Keefe DL. The cardiotoxic potential of the 5-HT(3) receptor antagonist anti- Mertens WC, Higby DJ, Brown D, et al. Improving the care of patients with regard
t e ro h
emetics: is there cause for concern? Oncologist. 2002;7(1):65-72. to chemotherapy-induced nausea and emesis: the effect of feedback to clinicians on
d.
adherence to antiemetic prescribing guidelines. J Clin Oncol. 2003;21(7):1373-1378.
8. Gralla RJ. Metoclopramide. A review of antiemetic trials. Drugs. 1983;25(suppl 1):
63-73. Navari RM. Role of neurokinin-1 receptor antagonists in chemotherapy-induced eme-
sis: summary of clinical trials. Cancer Invest. 2004;22(4):569-576.
ib
9. Slatkin NE. Cannabinoids in the treatment of chemotherapy-induced nausea
i te
and vomiting: beyond prevention of acute emesis. J Support Oncol. Schnell FM. Chemotherapy-induced nausea and vomiting: the importance of acute
d.
2007;5(5 suppl 3):1-9. antiemetic control. Oncologist. 2003;8(2):187-198.

Chemotherapy-Induced Table 1. Confounding Factors in Patients

Diarrhea: With Diarrhea
Diet
Treatment Guidelines High-fiber diet
Highly osmolar diet
Tyra Gatewood, PharmD, BCOP
Laxative abuse
Clinical Pharmacist
Milk or milk products
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida
Endocrine factors
A
ll
Hyperthyroidism
C ri
hemotherapy-induced diarrhea (CID) remains a
gh
Co es
Neuroendocrine tumors
significant public health problem. The most seri-
ts
py erv
r
ri
ous offenders are the cytotoxic drugs 5-fluorouracil Infection
gh d.
(5-FU) and irinotecan. It is well-known that CID can reduce Clostridium difficile
t
© ep
e
overall quality of life. In addition, CID has been shown to be Incident pathogens (Campylobacter, Escherichia coli,
2 0 ro
Bacillus cereus, Yersinia, Shigella, Salmonella)
R
associated with lethal toxicities, such as dehydration, elec-
08 du
M tio
trolyte imbalances, and ileus.
Inflammation
cM n
Reviewers analyzing excessive rates of early death in Crohn’s disease
ah in
c
2 large, cooperative group trials involving irinotecan and
on w
Diverticulitis
bolus 5-FU–leucovorin (IFL) reported that treatment-
Pu ol
Irritable bowel syndrome
bl e o
induced or -exacerbated deaths were most commonly the Radiation proctitis
is
h
hi
result of multiple concurrent toxicities: either a gastro- Ulcerative colitis
ng n p
intestinal (GI) syndrome characterized by watery diarrhea
G art
Malabsorption
ro
associated with cramping, fevers, leukopenia, and ulti-
up wit
Bowel wall edema
mately vascular collapse and death or a vascular syndrome
Motility disturbances
un ho
characterized by sudden and unexpected thromboembo-
le ut
Partial bowel obstruction
ss
lic events (some patients experienced both syndromes). Protein-losing enteropathy
ot rm
The panel concluded that close clinical monitoring, early Sprue
he
pe
recognition of toxicities and toxicity syndromes, aggres-
rw sio
is
sive therapeutic intervention, and early clinical interven- Drugs
is
e
no s p
tions in the presence of GI toxicities are recommended for Antibiotics
t e ro h
patients receiving IFL and other intensive chemotherapy Chemotherapy
d.
regimens associated with the GI syndrome.1 Laxatives/stool softeners
Monoclonal antibodies
In addition to being associated with mortality, CID poses
ib
i
a clinical challenge for clinicians. Patients who are respond-
te
d.
ing to treatment may require interruptions in therapy or
dose reductions. Quality-of-life impairment in patients
with even mild or moderate diarrhea may require them to
reschedule activities and curtail work, travel, or recreation.
They may require hospitalization or outpatient treatments.
Given that CID is such a widespread problem,2-20 effective

management has important public health implications.

Table 2. Agents for the
Clinical Assessment of CID Treatment of Diarrhea
The assessment of CID is often problematic in both
Adsorbents
the clinical and research settings. The best measurement Charcoal
of the intensity of diarrhea is a 72-hour stool collection Kaolin + pectin
with quantification of volume, but this remains impracti-
cal in the community setting and even in most research Anticholinergics
institutions. An alternative assessment of the severity Atropine
Belladonna
A
of diarrhea is symptom quantification. The most com-
ll
ri
monly used guidelines are the National Cancer Institute Antisecretory agents
gh
Co es
Common Toxicity Criteria (NCI-CTC), which assess symp-
ts
Bismuth subsalicylate
py erv
r
ri
toms on a scale of 1 to 4 (1, mild; 4, life-threatening or Octreotide
gh d.
disabling). Although useful, these criteria are limited by Sulfasalazine
t
© ep
e
certain ambiguities in interpretation. The guidelines are
2 0 ro
Opioids
R
based on changes from a patient’s baseline. If a patient
08 du
Diphenoxylate
M tio
with a colostomy has a baseline of X, then anything above
Tincture of opium
cM n
this would be a red flag that CID may be problematic. The
ah in
c
assessment and management of CID are further compli- Probiotic agents
on w
cated by the presence of confounding factors in patients Bifidobacterium
Pu ol
bl e o
with cancer (Table 1). Lactobacillus
is
h
hi
ng n p
Genetic Factors
G art
i
ro
Some patients have a genetic predisposition to the
up wit
development of increased toxicity from either 5-FU or Approximately 10% of the Caucasian population is
un ho
irinotecan. Patients with the inherited disorder dihydro- homozygous for the allele that causes this deficiency
le ut
ss
pyrimidine dehydrogenase deficiency (DPD) are unable (UGT1A1*28). Patients homozygous for the allele are at
ot rm
to adequately metabolize 5-FU. Approximately 3% of the risk for severe diarrhea and neutropenia following irinote-
he
pe
Caucasian population and 0.1% of the African American can administration. Testing for UGT1A1*28 is currently
rw sio
is
population possess this deficiency. These patients are at a available; however, the clinical usefulness of these results
is
e
no s p
higher risk for early, severe, and prolonged toxicities fol- is questionable. A recently published study conducted in
t e ro h
lowing 5-FU administration, including diarrhea, mucositis, pediatric patients reported that there was no correlation
d.
and neutropenia. Patients presenting with excessive tox- between UGT1A1*28 genotype and increased toxicity in
icity may be considered DPD-decificient. In these cases, patients receiving a protracted schedule of low-dose iri-
ib
i
significant dose reductions or omission of 5-FU as part of notecan. This study further reported that increased toxic-
te
d.
the treatment regimen is warranted. ity in patients with the UGT1A1*28 genotype was most
Gilbert syndrome, another inherited disorder, is charac- likely due to high SN-38 exposure, as is seen with higher
terized by a deficiency in uridine diphosphate glucuro- doses of irinotecan.21 However, until results from further
nosyltransferase activity (UGT1A1). UGT1A1 is responsible studies are available, an initial 20% dose reduction of iri-
for inactivating SN-38, the activate metabolite of irinote- notecan is recommended for patients with suspected or
can that is also responsible for causing the GI toxicity. known UGT1A1 deficiency. Further dose reductions or

First report of diarrhea: evaluate patient

• Obtain history of onset and duration of diarrhea Complicated
• Have patient describe number of stools and stool characteristics CTC grade 3 or 4 diarrhea or grade 1 or 2
(eg, watery, blood in stool, nocturnal) with 1 or more of the following:
• Assess for fever, dizziness, abdominal pain/cramping, weakness
• Cramping
(rule out risk for sepsis, bowel obstruction, dehydration)
• Obtain medication profile (to identify any diarrheogenic agents) • Nausea/vomiting (grade 2)
• Obtain dietary profile (to identify diarrhea-enhancing foods) • Decreased performance status
• Fever
• Sepsis
A
ll
• Neutropenia
Uncomplicated
ri
gh
• Frank bleeding
Co es
CTC grade 1 or 2 diarrhea with no Added risk factors
ts
py erv
complicating signs or symptoms • Dehydration
ri
gh d.
t
© ep
e
2 0 ro
Management
08 du
• Stop all lactose-containing products, alcohol, and highly
M tio
osmolar supplements
cM n
• Drink 8 to 10 large glasses of clear liquids per day (eg, Gatorade, broth)
ah in
c
• Eat frequent small meals (bananas, rice, applesauce, toast, plain pasta)
on w
• Instruct patient to record number of stools and report symptoms of
Pu ol
life-threatening sequelae (eg, fever, dizziness upon standing)
bl e o
• For grade 2 diarrhea, hold cytotoxic CT until symptoms resolve and
is
h
consider dose reduction
hi
ng n p
r
G art
i
ro
up wit
Treatment
un ho
Administer loperamide; initial dose 4 mg, followed by
le ut
2 mg q4h or after very unformed stool
ss
Progression to severe diarrhea
ot rm
(NCI grade 3 or 4 fever, dehydration,
he
neutropenia, blood in stool)
pe
rw sio
Reassess 12-24 h later Diarrhea unresolved
is
is
e
no s p
n
t e ro h
Diarrhea resolving/ Diarrhea/persistent diarrhea Reassess 12-24 h later
d.
resolved (NCI grade 1 or 2)
• Continue instructions for • Administer loperamide 2 mg q2h
ib
dietary modification • Start oral antibiotics
tei
• Gradually add solid foods • Observe patient for response
d.
to diet RT-induced: oral antibiotics not Figure. Guidelines for the evaluation and
• Discontinue loperamide after generally recommended
12-h diarrhea-free interval management of chemotherapy-induced
diarrhea.
Adapted from reference 34.

omission of irinotecan may be required based on patient

tolerance to treatment.22-25
Admit to hospitala
• Administer octreotide Management of CID
100-150 mcg SQ tid or
I.V. (25-50 mcg/h) if The treatment of CID depends on the overall severity of
dehydration severe, the problem as assessed by criteria such as the NCI-CTC.
with dose escalation
up to 500 mcg tid In addition to antidiarrheal agents (Table 2), patients with
• Start I.V. fluids and moderate to severe CID may require I.V. fluids in the outpa-
antibiotics as needed Evaluate in office or tient (day clinic) or inpatient setting. For patients with mod-
(eg, fluoroquinolone) outpatient center
A
erate to severe diarrhea and associated symptoms or signs
ll
• Stool workup, CBC, and • Check stool workupb
ri
electrolyte profile • Check CBC and such as fever, chills, and leukocytosis, the administration
gh
Co es
• Discontinue cytotoxic electrolytes of parenteral antibiotics should be considered. Attention
ts
py erv
CT until all symptoms • Perform abdominal
ri
should be given to modification of diet, with elimination of
gh d.
resolve; restart examination
CT at reduced dose milk products, fatty or greasy foods, high-fiber foods, and
t
• Replace fluids and
© ep
e
electrolytes highly osmolar supplements.
2 0 ro
as appropriate
08 du
• Discontinue loperamide; Antidiarrheal Agents
M tio
begin second-line
cM n
agent Synthetic opioids, such as loperamide, are the most com-
ah in
c
-Octreotide
monly used antidiarrheal agents because of their good
on w
SQ tid, with dose
side-effect profile and low cost. Loperamide is currently the
Pu ol
escalation up to
bl e o
500 mcg tid initial treatment of choice in the management of CID. For
is
h
Progression to -Other second-line agent
hi
severe diarrhea (eg, tincture of opium)
the treatment of mild diarrhea, standard-dose loperamide
ng n p
NCI grade 3 or 4 (4 mg initially, then 2 mg for each episode to a maximum
G art
± fever, dehydration,
ro
of 8 mg per day) is effective. However, clinically signifi-
up wit
neutropenia,
blood in stool cant diarrheal syndromes often require a more aggressive
un ho
double-dose strategy (4-mg initial dose, then 2 mg every
le ut
ss
2 hours until the patient is episode-free for 12 hours, with
Persistent diarrhea
ot rm
no maximum daily dose). Aggressive loperamide dosing,
he
NCI grade 1 or 2;
pe
especially in the setting of irinotecan-based therapy, is
rw sio
no fever, dehydration,
is
neutropenia, blood effective in minimizing grade 3 or 4 CID.26-28 This regimen
is
e
in stool
no s p
Diarrhea unresolved is effective as long as patients are thoroughly educated
t e ro h
about the dosing recommendations.
d.
CBC, complete blood cell count; CT, chemotherapy; CTC, Common Toxicity
The somatostatin analog octreotide also has demonstrat-
Criteria; NCI, National Cancer Institute; RT, radiotherapy; SQ, subcutaneously ed activity in the treatment of CID.29-31 A randomized trial
ib
i
a
For selected patients with chemotherapy-induced diarrhea, consider intensive conducted by Zidan and colleagues that studied octreotide
te
d.
outpatient management, unless the patient has sepsis, neutropenia, or fever.
b
100 mcg subcutaneously (SQ) 3 times daily reported reso-
Check for blood, fecal leukocytes, Clostridium difficile, Salmonella, Escherichia
coli, Campylobacter, infectious colitis. lution of grade 2 or 3 CID in 94% of patients.29 In a trial
conducted by Gebbia et al, 80% of patients who received
Figure. Guidelines for the evaluation and
octreotide 500 mcg SQ 3 times daily achieved complete
management of chemotherapy-induced diarrhea. resolution of grade 3 or 4 CID within 4 days of treatment.31
The long-acting formulation of octreotide (octreotide LAR)

was evaluated by Rosenoff and colleagues in the STOP notecan was associated with a reduction of GI adverse
(Sandostatin LAR Depot Trial for the Optimum Prevention effects, including diarrhea and nausea, and the combina-
of Chemotherapy-Induced Diarrhea) study.32 This study tion is being evaluated as second-line therapy in a Phase
compared 30 and 40 mg of octreotide LAR intramuscu- II trial.37 PHY906 (PhytoCeutica), a botanical drug used
larly every 28 days during chemotherapy. The differences frequently in the Far East, is currently being studied in a
in results between the 2 treatment groups were not sta- Phase I/IIA trial, but interest in this regimen appears to be
tistically significant. However, those patients receiving the limited because of its toxicity profile. There is also ongo-
40-mg dose reported fewer episodes of severe diarrhea. ing research using pasireotide (SOM230), a multiple-ligand
Although data documenting the activity of octreotide in somatostatin analog that exhibits high-affinity binding for
A
CID are increasing, it is still considered second-line therapy somatostatin-receptor subtypes sst1,2,3 and sst5. Results
ll
in this setting.32,33
ri
from a Phase II study using pasireotide in patients with
gh
Co es
metastatic carcinoid tumors reported a 25% efficacy rate
ts
py erv
Practice Guidelines
ri
in controlling symptoms that were inadequately controlled
gh d.
Definitive recommendations cannot be made until further by long-acting octreotide.38
t
© ep
e
trials have clarified the best treatment options. In the interim, One novel area of interest has been the use of probiot-
2 0 ro
R
guidelines for the management of CID were adopted in 1998
08 du
ics for the treatment of CID. These include Lactobacillus
M tio
by an expert panel convened for this task; updated guide- acidophilus and Bifidobacterium species, benign bacteria
cM n
lines were published in 2004.34 The guidelines (Figure) are that are administered orally and decrease the severity of
ah in
c
intended to improve the overall outcome of patients with diarrhea. Finally, although case reports and secondary
on w
CID and to prevent late catastrophic events. With irinotecan study end points have suggested that glutamine supple-
Pu ol
bl e o
as a component of first-line therapy, future research into mentation during chemotherapy or radiotherapy may help
is
h
hi
the mechanisms and management of CID will continue to to diminish the incidence of CID, trial results have been
ng n p
be warranted. mixed, and the efficacy of glutamine in reducing CID is still
G art
i
ro
unknown. Future research is needed to clarify its role in the
up wit
Future Directions management of patients with cancer.39-43
un ho
Future CID research will focus on a number of new direc-
le ut
Conclusion
ss
tions. One area of interest is determining the pathophysiol-
ot rm
ogy of irinotecan-induced diarrhea and how it differs from
he
In summary, CID is a significant clinical problem, and one
pe
that of 5-FU. A report from Japan has suggested a poten-
rw sio
that may be overlooked by the busy clinician. Recent pub-
is
tial novel mechanism involving ß-glucuronidase activity in
is
e
lications have drawn attention to this problem and have
no s p
intestinal microflora.35 To date, however, antibiotic therapy resulted in increased recognition of the syndrome. Newer
t e ro h
has not been successful in reducing irinotecan-induced
d.
strategies and more effective agents are being developed
diarrhea in humans. to reduce the morbidity and mortality associated with CID.
In addition to octreotide, several other agents are being
ib
i
explored to treat irinotecan-induced diarrhea. The cyclo-
te
References
d.
oxygenase-2 inhibitor celecoxib (Celebrex, Merck) has been
studied in a mouse tumor model and was shown to enhance 1. Rothenberg ML, Meropol NJ, Poplin EA, Van Custem E, Wadler S. Mortality asso-
the antitumor effect of irinotecan against an explanted human ciated with irinotecan plus bolus fluorouracil/leucovorin: summary findings of an
independent panel. J Clin Oncol. 2001;19:3801-3807.
colon cancer and to reduce the severity of irinotecan-asso-
2. Ardavanis A, Extra JM, Espie M, et al. Phase II trial of a combination of vinorel-
ciated diarrhea.36 In a pilot study of patients with metastatic bine, cyclophosphamide and 5-fluorouracil in the treatment of advanced breast
colorectal cancer, thalidomide in combination with iri- cancer. In Vivo. 1998;12:559-562.

3. Ito Y, Mukaiyama T, Ogawa M, et al. Epirubicin-containing high-dose chemothera- 19. Mani S, Kugler JW, Sciortino DF, et al. Phase II trial of uracil/tegafur (UFT) plus
py followed by autologous hematopoietic progenitor cell transfusion for patients leucovorin in patients with advanced pancreatic carcinoma: a University of Chicago
with chemotherapy-sensitive metastatic breast cancer: results of 5-year follow- Phase II consortium study. Ann Oncol. 1998;9:1035-1037.
up. Cancer Chemother Pharmacol. 1999;43:8-12.
20. O’Connell MJ, Martenson JA, Wieand HS, et al. Improving adjuvant therapy for
4. Papadopoulos KP, Garvin JH, Fetell M, et al. High-dose thiotepa and etoposide- rectal cancer by combining protracted-infusion fluorouracil with radiation thera-
based regimens with autologous hematopoietic support for high-risk or recurrent py after curative surgery. N Engl J Med. 1994;331:502-507.
CNS tumors in children and adults. Bone Marrow Transplant. 1998;22:661-667.
21. Stewart CF, Panetta JC, O’Shaugnessy MA, et al. UGT1A1 promoter genotype cor-
5. Leichman CG, Fleming TR, Muggia FM, et al. Phase II study of fluorouracil and its relates with SN-38 pharmacokinetics, but not severe toxicity in patients receiving
modulation in advanced colorectal cancer: a Southwest Oncology Group study. low-dose irinotecan. J Clin Oncol. 2007;25:2594-2600.
J Clin Oncol. 1995;13:1303-1311.
22. Schmoll HJ, Cartwright T, Tabernero J, et al. Phase III trial of capecitabine plus
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ri
Chemother Pharmacol. 1998;42:336-340.
gh
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23. Camptosar product information. New York, NY: Pfizer Inc; July 2005.
ts
7. Nobile MT, Barzacch MC, Sanguineti O, et al. Activity of high-dose 24-hour
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24. Iyer L, King CD, Whitington PF, et al. Genetic predisposition to the metabolism of
5-fluorouracil infusion plus L-leucovorin in advanced colorectal cancer.
ri
irinotecan (CPT-11). J Clin Invest. 1998;101:847-854.
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Anticancer Res. 1998;18(1B):517-521.
t
25. Wasserman E, Myara A, Lokiec F, et al. Severe CPT-11 toxicity in patients with
© ep
8. Nogue M, Segui MA, Saigi E, et al. Protracted treatment with tegafur and low-
e
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2 0 ro
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08 du
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9. Saliba F, Hagipantelli R, Misset JL, et al. Pathophysiology and therapy of irinote-
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is
h
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hi
11. Cunningham D, Pyrhonen S, James RD, et al. Randomised trial of irinotecan plus
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supportive care versus supportive care alone after fluorouracil failure for patients 29. Zidan J, Haim N, Beny A, Stein M, Gez E, Kuten A. Octreotide in the treatment of
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ro
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American Society of Clinical Oncology; June 2-6, 2006; Atlanta, GA. Abstract 171.
_____________________________________________
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fluorouracil-induced intestinal toxicity: a double blind, placebo controlled,
randomised trial. Gut. 2001;48:28-33.
_____________________________________________
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41. Kozelsky TF, Meyers GE, Sloan JA, et al, for the North Central Cancer Treatment
ri
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Group. Phase III double-blind study of glutamine versus placebo for the preven-
tion of acute diarrhea in patients receiving pelvic radiation therapy. J Clin Oncol. _____________________________________________
ts
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2003;21:1669-1674.
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42. Bozzetti F, Biganzoli L, Gavazzi C, et al. Glutamine supplementation in cancer _____________________________________________
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patients receiving chemotherapy: a double-blind randomized study. Nutrition.
2 0 ro
1997;13:748-751.
_____________________________________________
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43. Ziegler TR. Glutamine supplementation in cancer patients receiving bone marrow
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transplantation and high dose chemotherapy. J Nutr. 2001;131(9 suppl):2578S-
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Cancer Support 2009

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Cancer Support 2009

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newly approved treatment options. The guidelines in this sec-

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defined by scientific reports; however, the Oncology Nursing

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5-FU, 5-fluorouracil DMA, N,N-dimethylacetamide

CYP, cytochrome P-450 tiw, 3 times weekly

D5W, 5% dextrose in water UTI, urinary tract infection

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Alemtuzumab Arsenic trioxide

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Asparaginase–Escherichia coli strain Bevacizumab

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nausea, vomiting, dehydration, ileus, neuropathy (sensory), neuro-

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Bortezomib Busulfan injection

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Carboplatin Carmustine for injection (BCNU)

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artery disease, CHF, or arrhythmias. Close monitoring of serum

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ototoxicity, which is more pronounced in children and is manifested

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Daunorubicin citrate liposome injection Daunorubicin HCl

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Denileukin diftitox Docetaxel

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Doxorubicin Doxorubicin HCl liposome injection

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5-Fluorouracil (5-FU) Fulvestrant

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Gemcitabine Gemtuzumab ozogamicin

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Goserelin Ibritumomab tiuxetan and indium-111 (In-111)/

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be administered to patients with ≥25% lymphoma marrow involve-

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Ifosfamide Interferon alfa-2a (recombinant)

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Interferon alfa-2b (recombinant) Irinotecan

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necrosis, erythema multiforme, pruritus, urticaria, photosensitivity,

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Paclitaxel protein-bound particles Panitumumab

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Pegaspargase [PEG-L-asparaginase] Pemetrexed

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Comments—Dose reductions for grade 3/4 toxicity are outlined

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abdominal pain should prompt a thorough diagnostic evaluation

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