Antineoplastic Agents

Glossary of Key Terms

 alopecia: hair loss; a common adverse effect of many antineoplastic drugs, which are more
effective against rapidly multiplying cells such as those of hair follicles
 anaplasia: loss of organization and structure; property of cancer cells
 angiogenesis: the generation of new blood vessels; cancer cells release an enzyme that will
cause angiogenesis or the growth of new blood vessels to feed the cancer cells
 antineoplastic agent: drug used to combat cancer or the growth of neoplasms
 autonomy: loss of the normal controls and reactions that inhibit growth and spreading; property
of cancer cells
 bone marrow suppression: inhibition of the blood-forming components of the bone marrow; a
common adverse effect of many antineoplastic drugs, which are more effective against rapidly
multiplying cells, such as those in bone marrow; also seen in anemia, thrombocytopenia, and
leukopenia
 carcinoma: tumor that originates in epithelial cells
 metastasis: ability to enter the circulatory or lymphatic system and travel to other areas of the
body that are conducive to growth and survival; property of cancer cells
 neoplasm: new or cancerous growth; occurs when abnormal cells have the opportunity to
multiply and grow
 sarcoma: tumor that originates in the mesenchyme and is made up of embryonic connective
tissue cells
CANCER

- A disease that can strike a person at any age. It remains second

only to coronary disease as the leading cause of death in the
United States.
- Treatment of cancer can be prolonged and often debilitating.
The patient can experience numerous and wide-ranging
complications and effects.
- All cancers start with a single cell that is genetically different
from the other cells in the surrounding tissue. This cell divides,
passing along its abnormalities to daughter cells, eventually
producing a tumor or neoplasm that has characteristics quite
different from those of the original tissue (Figure 14.1).
- As the abnormal cells continue to divide, they lose more and
more of their original cell characteristics. The cancerous cells
exhibit anaplasia—a loss of cellular differentiation and
organization, which leads to a loss of their ability to function
normally.
- They also exhibit autonomy, growing without the usual
homeostatic restrictions that regulate cell growth and control.
This loss of control allows the cells to form a tumor.
- Over time, these neoplastic cells grow uncontrollably, invading
and damaging healthy tissue in the area and even undergoing
metastasis, or traveling from the place of origin to develop new
tumors in other areas of the body where conditions are
favorable for cell growth

A. Causes of Cancer
 Definite genetic link
 Viral Infection
 Constant irritation
 Cell turnover
 Stress
 Pipe smokers
 People living in areas with carcinogenic or cancer-causing chemicals in the air,
water, or even the ground

B. Types of Cancer
1. Solid Tumor: Originate in any body organ and may be further divided into carcinomas,
or tumors that originate in epithelial cells, and sarcomas, or tumors that originate in the
mesenchyme and are made up of embryonic connective tissue cells. Examples of
carcinomas include granular cell tumors of the breast, bronchogenic tumors arising in
cells that line the bronchial tubes, and squamous and basal tumors of the skin. Sarcomas
 include osteogenic tumors, which form in the primitive cells of the bone, and
rhabdomyosarcomas, which occur in striated muscles
2. Hematological Malignancies: Such as the leukemias and lymphomas, which occur in the
blood-forming organs. Involve the blood-forming organs of the body, the bone marrow,
and the lymphatic system. These malignancies alter the body’s ability to produce and
regulate the cells found in the blood.

ANTINEOPLASTIC DRUGS

- Can work by affecting cell survival or by boosting the immune system in its efforts to combat the
abnormal cells (Figure 14.3).
- Commonly used today include alkylating agents, antimetabolites, antineoplastic antibiotics,
mitotic inhibitors, hormones and hormone modulators, cancer cell–specific agents, protein
tyrosine kinase inhibitors (which target enzymes specific to the cancer cells), and a group of
antineoplastic agents that cannot be classified elsewhere. Other drugs are used to combat the
serious adverse effects that can be associated with the antineoplastic drugs. These drugs are
used as adjunctive therapy. Figure 14.4 shows sites of action of these drugs. Box 14.1 discusses
use of these drugs across the lifespan
 - Adverse Effects: Toxic effects on ova and sperm production affecting person’s fertility;
Jeopardize the immune system by causing bone marrow suppression, inhibiting the blood-
forming components of the bone marrow and interfering with the body’s normal protective
actions against abnormal cells; Experience hair and/or skin effects as these cells are rapidly
turning over cells

ALKYLATING AGENTS

- Can affect cells even in the resting phase, these drugs are said to be non–cell cycle specifi c
(Figure 14.4).
- They are most useful in the treatment of slow-growing cancers, which have many cells in the
resting phase.
- Alkylating agents (Table 14.1) include the following drugs: altretamine (Hexalen), bendamustine
(Treanda), busulfan (Busulfex, Myleran), carboplatin (Paraplatin), carmustine (BiCNU, Gliadel),
chlorambucil (Leukeran), cisplatin (Platinol-AQ), cyclophosphamide (Cytoxan, Neosar),
dacarbazine (DTIC-Dome), ifosfamide (Ifex), lomustine (CeeNU), mechlorethamine (Mustargen),
melphalan (Alkeran), oxaliplatin (Eloxatin), procarbazine (Matulane), streptozocin (Zanosar),
temozolomide (Temodar), and thiotepa (Thioplex).
Therapeutic Actions and Indications

 Alkylating agents produce their cytotoxic effects by reacting chemically with portions of
the RNA, DNA, or other cellular proteins, being most potent when they bind with
cellular DNA.
 The oldest drugs in this class are the nitrogen mustards, and modifi cations of the
structure of these drugs have led to the development of the nitrosoureas.
 These drugs are most useful in the treatment of slow-growing cancers such as various
lymphomas, leukemias, myelomas, some ovarian, testicular, and breast cancers, and
some pancreatic cancers. See Table 14.1 for usual indications for each of the alkylating
agents. These agents are not used interchangeably.

Pharmacokinetics
  The alkylating agents vary in their degree of absorption, and little is known about their
distribution in the tissues.
 They are metabolized and sometimes activated in the liver, with many of these agents
using the cytochrome P450 systems.
 They are excreted in the urine.

Contraindications and Cautions

 Alkylating agents are contraindicated during pregnancy and lactation due to their
potential for severe effects on the fetus and neonate.
 Caution is necessary when giving alkylating agents to any individual with a known
allergy to any of them; with bone marrow suppression, which is often the index for
redosing and dosing levels; or with suppressed renal or hepatic function, which may
interfere with metabolism or excretion of these drugs and often indicates a need to
change the dose.

Adverse Effects

 Adverse effects frequently encountered with the use of these alkylating agents are listed
here; see Table 14.1 for a list of adverse effects specifi c to each agent.
 Amifostine (Ethyol) and mesna (Mesnex) are cytoprotective (cellprotecting) drugs that
may be given to limit certain effects of cisplatin and ifosfamide, respectively (Box 14.3).
Hematological effects include bone marrow suppression, with leukopenia,
thrombocytopenia, anemia, and pancytopenia, secondary to the effects of the drugs on
the rapidly multiplying cells of the bone marrow.
 GI effects include nausea, vomiting, anorexia, diarrhea, and mucous membrane
deterioration, all of which are related to the drugs’ effects on the rapidly multiplying
cells of the GI tract.
 Hepatic toxicity and renal toxicity may occur, depending on the exact mechanism of
action.
 Alopecia, or hair loss, related to effects on the hair follicles, may also occur.
 All drugs that cause cell death can cause a potentially toxic increase in uric acid levels.
Allopurinol has been used to help alleviate this problem and in 2004, a new drug,
rasburicase, was introduced to manage uric acid levels in pediatric patients (Box 14.4).

Clinically Important Drug–Drug Interactions

 Alkylating agents that are known to cause hepatic or renal toxicity should be used
cautiously with any other drugs that have similar effects. In addition, drugs that are toxic
to the liver may adversely affect drugs that are metabolized in the liver or that act in the
liver (e.g., oral anticoagulants). Always check for specific drug–drug interactions for each
agent in a nursing drug guide.

ANTIMETABOLITES
- drugs that have chemical structures similar to those of various natural metabolites that are
necessary for the growth and division of rapidly growing neoplastic cells and normal cells.
- Antimetabolites include capecitabine (Xeloda), cladribine (Leustatin), clofarabine (Clolar),
cytarabine (DepoCyt, Tarabine PFS), fl oxuridine (FUDR), fl udarabine (Fludara), fl uorouracil
(Adrucil, Carac, Efudex, Fluoroplex), gemcitabine (Gemzar), mercaptopurine (Purinethol),
methotrexate (Rheumatrex, Trexall), pemetrexed (Alimta), pentostatin (Nipent), pralatrexate
(Folotyn), and thioguanine (Tabloid).
Therapeutic Actions and Indications

 Antimetabolites inhibit DNA production in cells that depend on certain natural

metabolites to produce their DNA.
 They replace these needed metabolites and thereby prevent normal cellular function.
 Many of these agents inhibit thymidylate synthetase, DNA polymerase, or folic acid
reductase, all of which are needed for DNA synthesis. They are considered to be S phase
specifi c in the cell cycle. T
 hey are most effective in rapidly dividing cells, preventing cell replication, and leading to
cell death (Figure 14.5).
 The antimetabolites are indicated for the treatment of various leukemias and some GI
and basal cell cancers (see Table 14.2 for usual indications for each agent). Use of these
drugs has been somewhat limited because neoplastic cells rapidly develop resistance to
these agents. For this reason, these drugs are usually administered as part of a
combination therapy.

Pharmacokinetics

 Methotrexate is absorbed well from the GI tract and is excreted unchanged in the
urine. Patients with renal impairment may require reduced dose and increased
monitoring when taking methotrexate. Methotrexate readily crosses the blood–brain
barrier.
 Cytarabine, clofarabine, fl oxuridine, fluorouracil, gemcitabine, fl oxuridine,
pralatrexate, and pemetrexed are not absorbed well from the GI tract and need to be
administered parenterally. They are metabolized in the liver and excreted in the urine,
 necessitating close monitoring of patients with hepatic or renal impairment who are
receiving these drugs.
 Mercaptopurine and thioguanine are absorbed slowly from the GI tract and are
metabolized in the liver and excreted in the urine.

Contraindications and Cautions

 Antimetabolites are contraindicated for use during pregnancy and lactation because of
the potential for severe effects on the fetus and neonate.
 Caution is necessary when administering antimetabolites to any individual with a
known allergy to any of them to prevent hypersensitivity reactions; with bone marrow
suppression, which is often the index for redosing and dosing levels; with renal or
hepatic dysfunction, which might interfere with the metabolism or excretion of these
drugs and often indicates a need to change the dose; and with known GI ulcerations or
ulcerative diseases that might be exacerbated by the effects of these drugs.

Adverse Effects

 Adverse effects frequently encountered with the use of the antimetabolites are listed
here. To counteract the effects of treatment with one antimetabolite— methotrexate
— the drug leucovorin or its isomer levoleucovorin is sometimes given (Box 14.7).
 Hematological effects include bone marrow suppression, with leukopenia,
thrombocytopenia, anemia, and pancytopenia, secondary to the effects of the drugs on
the rapidly multiplying cells of the bone marrow.
 Toxic GI effects include nausea, vomiting, anorexia, diarrhea, and mucous membrane
deterioration, all of which are related to drug effects on the rapidly multiplying cells of
the GI tract.
 CNS effects include headache, drowsiness, aphasia, fatigue, malaise, and dizziness.
Patients should be advised to take precautions if these conditions occur. There is a risk
of pulmonary toxicity, including interstitial pneumonitis with these drugs. As with
alkylating agents, effects of the antimetabolites may include possible hepatic or renal
toxicity, depending on the exact mechanism of action. Alopecia may also occur (Figure
14.6).

Clinically Important Drug–Drug Interactions

 Antimetabolites that are known to cause hepatic or renal toxicity should be used with
care with any other drugs known to have the same effect.In addition, drugs that are
toxic to the liver may adversely affect drugs that are metabolized in the liver or that act
in the liver (e.g., oral anticoagulants). Check for specific drug–drug interactions for each
agent in a nursing drug guide.
ANTINEOPLASTIC ANTIBIOTICS

- Are also toxic to human cells. Because these drugs tend to be more toxic to cells that are
multiplying rapidly, they are more useful in the treatment of certain cancers.
- Antineoplastic antibiotics include bleomycin (Blenoxane), dactinomycin (Cosmegen),
daunorubicin (DaunoXome), doxorubicin (Adriamycin, Doxil), epirubicin (Ellence), idarubicin
(Idamycin), mitomycin (Mutamycin), mitoxantrone (Novantrone), and valrubicin (Valstar).
Therapeutic Actions and Indications

 Some antineoplastic antibiotics break up DNA links, and others prevent DNA synthesis.
 The antineoplastic antibiotics are cytotoxic and interfere with cellular DNA synthesis by
inserting themselves between base pairs in the DNA chain. This, in turn, causes a
mutant DNA molecule, leading to cell death (Figure 14.4). See Table 14.3 for usual
indications for each antineoplastic antibiotic.
 Like other antineoplastics, the main adverse effects of these drugs are seen in cells that
multiply rapidly, such as those in the bone marrow, GI tract, and skin.
 Their potentially serious adverse effects may limit their usefulness in patients with
preexisting diseases and in those who are debilitated and, therefore, more susceptible
to these effects.

Pharmacokinetics

 The antineoplastic antibiotics are not absorbed well from the GI tract. They are given
intravenously (IV) or injected into specifi c sites.
 They are metabolized in the liver and excreted in the urine at various rates.
 Many of them have very long half-lives (e.g., 45 hours for idarubicin; more than 5 days
for mitoxantrone).
 Daunorubicin and doxorubicin do not cross the blood–brain barrier, but they are widely
distributed in the body and are taken up by the heart, lungs, kidneys, and spleen. This
can lead to toxic effects in these organs.

Contraindications and Cautions

 All of these agents are contraindicated for use during pregnancy and lactation because
of the potential risk to the fetus and neonate.
 Use caution when giving antineoplastic antibiotics to an individual with a known allergy
to the antibiotic or related antibiotics, to prevent hypersensitivity reactions.
 Care is necessary when administering these agents to patients with the following
conditions: bone marrow suppression, which is often the index for redosing and dosing
 levels; suppressed renal or hepatic function, which might interfere with the
metabolism or excretion of these drugs and often indicates a need to change the dose;
known GI ulcerations or ulcerative diseases, which may be exacerbated by the effects
of these drugs; pulmonary problems with bleomycin or mitomycin, or cardiac problems
with idarubicin or mitoxantrone, which are specifi cally toxic to these organ systems.

Adverse Effects

 Adverse effects frequently encountered with the use of these antibiotics include bone
marrow suppression, with leukopenia, thrombocytopenia, anemia, and pancytopenia,
secondary to the effects of the drugs on the rapidly multiplying cells of the bone
marrow.
 Toxic GI effects include nausea, vomiting, anorexia, diarrhea, and mucous membrane
deterioration, all of which are related to drug effects on the rapidly multiplying cells of
the GI tract.
 As with the alkylating agents and antimetabolites, effects of antineoplastic antibiotics
may include renal or hepatic toxicity, depending on the exact mechanism of action.
Alopecia may also occur.
 Specific antineoplastic antibiotics are toxic to the heart and lungs. Box 14.9 discusses a
cardioprotective drug that interferes with the effects of doxorubicin.

Clinically Important Drug–Drug Interactions

 Antimetabolites that are known to cause hepatic or renal toxicity should be used with
care with any other drugs known to have the same effect.
 Drugs that result in toxicity to the heart or lungs should be used with caution with any
other drugs that produce that particular toxicity. Check for specific drug–drug
interactions for each agent in a nursing drug guide.

MITOTIC INHIBITORS

- are drugs that kill cells as the process of mitosis begins (see Figure 14.5). These cell cycle–specifi
c agents inhibit DNA synthesis.
- Like other antineoplastics, the main adverse effects of the mitotic inhibitors occur with cells that
rapidly multiply: those in the bone marrow, GI tract, and skin.
- Mitotic inhibitors include cabazitaxel (Jevtana), docetaxel (Taxotere), etoposide (Toposar,
VePesid), ixabepilone (Ixempra), paclitaxel (Abraxane, Onxol, Taxol), teniposide (Vumon),
vinblastine (Velban), vincristine (Oncovin, Vincasar), and vinorelbine (Navelbine).
Therapeutic Actions and Indications

 The mitotic inhibitors interfere with the ability of a cell to divide; they block or alter DNA
synthesis, thus causing cell death.
 They work in the M phase of the cell cycle. These drugs are used for the treatment of a variety
of tumors and leukemias. See Table 14.4 for usual indications for each of these agents.

Pharmacokinetics

 Generally, these drugs are given intravenously because they are not well absorbed from the GI
tract.
 They are metabolized in the liver and excreted primarily in the feces, making them safer for use
in patients with renal impairment than the antineoplastics that are cleared through the kidney.

Contraindications and Cautions

 These drugs should not be used during pregnancy or lactation because of the potential risk to
the fetus or neonate.
 Use caution when giving these drugs to anyone with a known allergy to the drug or related
drugs to decrease the risk of serious hypersensitivity reactions.
 Care is necessary for patients with the following conditions: bone marrow suppression, which is
often the index for redosing and dosing levels; renal or hepatic dysfunction, which could
interfere with the metabolism or excretion of these drugs and often indicates a need to change
the dose; and known GI ulcerations or ulcerative diseases, which may be exacerbated by the
effects of these drugs.

Adverse Effects

 Adverse effects frequently encountered with the use of mitotic inhibitors include bone marrow
suppression, with leukopenia, thrombocytopenia, anemia, and pancytopenia, secondary to the
effects of the drugs on the rapidly multiplying cells of the bone marrow.
 GI effects include nausea, vomiting, anorexia, diarrhea, and mucous membrane deterioration. As
with the other antineoplastic agents, effects of the mitotic inhibitors may include possible
hepatic or renal toxicity, depending on the exact mechanism of action. Alopecia may also occur.
These drugs also cause necrosis and cellulitis if extravasation occurs, so it is necessary to
regularly monitor injection sites and take appropriate action as needed.

Clinically Important Drug–Drug Interactions

 Mitotic inhibitors that are known to be toxic to the liver or the CNS should be used with care
with any other drugs known to have the same adverse effect.
 Check specific drug–drug interactions for each agent in a nursing drug guide.
HORMONES AND HORMONE MODULATORS

- Some cancers, particularly those involving the breast tissue, ovaries, uterus, prostate, and
testes, are sensitive to estrogen stimulation.
- Estrogen-receptor sites on the tumor react with circulating estrogen, and this reaction
stimulates the tumor cells to grow and divide.
- Several antineoplastic agents are used to block or interfere with these receptor sites to prevent
growth of the cancer and in some situations to actually cause cell death. Some hormones are
used to block the release of gonadotropic hormones in breast or prostate cancer if the tumors
are responsive to gonadotropic hormones. Others may block androgen-receptor sites directly
and are useful in the treatment of advanced prostate cancers.
- Hormones and hormone modulators include anastrazole (Arimidex), bicalutamide (Casodex),
degarelix (Degarelix for Injection), estramustine (Emcyt), exemestane (Aromasin), fl utamide
(generic), fulvestrant (Faslodex), goserelin (Zoladex), histrelin (Vantas), letrozole (Femara),
leuprolide (Lupron, Eligard), megestrol (Megace), mitotane (Lysodren), nilutamide (Nilandron),
tamoxifen (Soltamox), toremifene (Fareston), and triptorelin pamoate (Trelstar Depot) (Table
14.5)
Therapeutic Actions and Indications

 The hormones and hormone modulators used as antineoplastics are receptor-site

specific or hormone specifi c to block the stimulation of growing cancer cells that are
sensitive to the presence of that hormone (see Figure 14.4).
 These drugs are indicated for the treatment of breast cancer in postmenopausal women
or in other women without ovarian function. Some drugs are indicated for the
treatment of prostatic cancers that are sensitive to hormone manipulation.

Pharmacokinetics

 These drugs are readily absorbed from the GI tract, metabolized in the liver, and
excreted in the urine.
 Caution must be used with any patient who has hepatic or renal impairment. These
drugs cross the placenta and enter into breast milk.

Contraindications and Cautions

 These drugs are contraindicated during pregnancy and lactation because of toxic effects
on the fetus and neonate.
 Hypercalcemia is a contraindication to the use of toremifene, which is known to
increase calcium levels. Use caution when giving hormones and hormone modulators to
anyone with a known allergy to any of these drugs to prevent hypersensitivity reactions.
 Care is necessary in patients with bone marrow suppression, which is often the index for
redosing and dosing levels, and in those with renal or hepatic dysfunction, which could
interfere with the metabolism or excretion of these drugs and often indicates a need to
change the dose.

Adverse Effects

 Adverse effects frequently encountered with the use of these drugs involve the effects
that are seen when estrogen is blocked or inhibited.
 Menopause-associated effects include hot flashes, vaginal spotting, vaginal dryness,
moodiness, and depression. Other effects include bone marrow suppression and GI
toxicity, including hepatic dysfunction.
 Hypercalcemia is also encountered as the calcium is pulled out of the bones without
estrogen activity to promote calcium deposition. Many of these drugs increase the risk
for cardiovascular disease because of their effects on the body.
 Clinically Important Drug–Drug Interactions

 If hormones and hormone modulators are taken with oral anticoagulants, there is often
an increased risk of bleeding.
 Care is also necessary when administering these agents with any drugs that might
increase serum lipid levels.

CANCER CELL–SPECIFIC AGENTS

- The goal of much of the current antineoplastic drug research is directed at fi nding drugs that
are cancer cell specific.
- These drugs would not have the devastating effects on healthy cells in the body and would be
more effective against particular cancer cells. T
- hree groups of drugs are available for cancer cell–specifi c actions: protein tyrosine kinase
inhibitors, an epidermal growth factor inhibitor, and a proteasome inhibitor (Table 14.6).
1. PROTEIN TYROSINE KINASE INHIBITORS
The protein kinase inhibitors (Table 14.6) act on specific enzymes that are needed for
protein building by specific tumor cells.
Blocking of these enzymes inhibits tumor cell growth and division.
Each drug that has been developed inhibits a very specific protein kinase and acts on
very specific tumors. T
hey do not affect healthy human cells, so the patient does not experience the numerous
adverse effects associated with antineoplastic chemotherapy.
Imatinib (Gleevec), the first drug approved in this class, is given orally and is approved to
treat chronic myelocytic leukemia (CML). Patients who have CML and who have been
switched to imatinib after traditional chemotherapy have been amazed at how good
they feel and how much they have recovered from the numerous adverse effects of the
traditional chemotherapy. Long-term effects are not yet known because the drug is
relatively new. Unfortunately, this drug is expensive. It is estimated that 1 year of
treatment with the drug (which needs to be taken continually) costs the patient
between $30,000 and $35,000. Novartis, the drug company that manufactures Gleevec,
has set up a patient assistance program with a sliding-scale price reduction based on
 income. They do not want patients to have to pay more than 20% of their annual
income for the drug. Patients prescribed this drug may need support and assistance in
obtaining financial help.
The protein tyrosine kinase inhibitors that are available include everolimus (Afi nitor),
gefi tinib (Iressa), imatinib (Gleevec), lapatinib (Tykerb), nilotinib (Tasigna), pazopanib
(Vorient), sorafenib (Nexavar), sunitinib (Sutent), and temsirolimus (Torisel).

2. EPIDERMAL GROWTH FACTOR INHIBITOR

In late 2004, the U.S. Food and Drug Administration (FDA) approved erlotinib
(Tarceva), a drug that inhibits cell epidermal growth factor receptors. This growth
factor is found on normal and cancerous cells but is more abundant on rapidly
growing cells.

3. PROTEASOME INHIBITOR
In 2003, the FDA approved bortezomib (Velcade) for the treatment of multiple
myeloma in patients whose disease had progressed after two other standard
therapies. This drug inhibits proteasome in human cells, a large protein complex
that works to maintain cell homeostasis and

Therapeutic Actions and Indications

 Imatinib is an oral antineoplastic drug is a protein tyrosine kinase inhibitor that

selectively inhibits the Bcr-Abl tyrosine kinase created by the Philadelphia chromosome
abnormality in CML. Blocking this enzyme inhibits proliferation and induces cell division
in Bcr-Abl–positive cell lines, as well as in new leukemic cells, thereby inhibiting tumor
growth in CML patients in blast crisis. It also inhibits a specific receptor site in
gastrointestinal stromal tumor patients. Because of its specific effects on these tumor
cells, it is not associated with adverse effects on normal human cells.
 Gefitinib, lapatinib, nilotinib, pazopanib, sorafenib, sunitinib, and temsirolimus work by
inhibiting various kinases in the cancer cell. Table 14.6 shows usual indications for all
protein tyrosine kinase inhibitors.

Pharmacokinetics

 Imatinib is slowly absorbed from the GI tract, reaching peak levels in 2 to 4 hours. It is
extensively metabolized in the liver, with a half-life of 18 and then 40 hours.
 Gefitinib is slowly absorbed from the GI tract, reaching peak levels in 3 to 7 hours. It is
metabolized in the liver with a half-life of 48 hours.
 Lapatinib, given orally, is absorbed from the GI tract, reaching peak levels in 1 to 1.5
hours. Lapatinib is metabolized in the liver, with a half-life of 24 hours.
 Nilotinib, given orally, reach peak levels in 3 hours after GI absorption. Most of the drug
is excreted unchanged in the stool with a half-life of 17 hours.
 Pazopanib is given orally, reaching peak levels in 2 to 4 hours; it is metabolized in the
liver and excreted in the feces, with a half-life of 30/9 hours.
  Sorafenib is well absorbed from the GI tract after oral administration, reaching peak
levels in 1 to 2 hours. Most of the drug is excreted unchanged in the stool with a half-life
of 24 to 48 hours.
 Sunitinib, given orally, is slowly absorbed from the GI tract, reaching peak levels in 6 to
12 hours. After metabolism in the liver, it has a half-life of 40 to 60 hours and then 80 to
110 hours for its active metabolite.
 Temsirolimus, only available for IV use, reaches peak levels at the end of the infusion. It
is metabolized in the liver and primarily excreted in the feces with a half-life of 17 hours
and then 55 hours for its active metabolite.
 Erlotinib is well absorbed orally from the GI tract, reaching peak levels in 4 hours. It is
metabolized in the liver with a half-life of 36 hours.
 Bortezomib, given IV, reaches peak effects at the end of the infusion. It is metabolized in
the liver and has a half-life of 40 to 193 hours.

Contraindications and Cautions

 All of these drugs are in pregnancy category D. Women of childbearing age should be
advised to use barrier contraceptives while taking this drug. It can enter breast milk, and
it should be used during lactation only if the benefits to the mother clearly outweigh the
risks to the baby. With imatinib and pazopanib caution should be used in patients with
known hepatic dysfunction.
 Nilotinib is contraindicated with patients who have or who are at risk for prolonged QT
intervals (hypokalemia, hypomagnesia, or taking another drug that prolongs the QT
interval) because it prolongs the QT interval, and sudden deaths could occur. These
drugs should not be given to anyone who has a history of hypersensitivity to any
component of the drug being given.

Adverse Effects

 The adverse effects associated with imatinib include GI upset, muscle cramps, heart
failure, fluid retention, and skin rash. The severe bone marrow suppression, alopecia,
and severe GI effects associated with more traditional antineoplastic therapy do not
occur.
 Gefitinib has been associated with potentially severe interstitial lung disease and various
eye symptoms.
 Nilotinib causes prolonged QT intervals and can impair liver and kidney function.
 Pazopanib is associated with some bone marrow depression, diarrhea, hypertension,
and liver impairment. Patients might also experience a change in hair color.
 Lapatinib causes diarrhea and can cause liver impairment and alter heart function.
 Erlotinib and bortezomib are associated with cardiovascular events and pulmonary
toxicity.
 Bortezomib has also been associated with peripheral neuropathy and liver and kidney
impairment.

Clinically Important Drug–Drug Interactions

  Use caution when administering imatinib with other drugs affected by the cytochrome
P450 enzyme system. In addition, St. John’s wort decreases the effectiveness of many of
these drugs and should be avoided.
 When using nilotinib avoid any other drugs that are known to prolong the QT interval
Clinically Important Drug–Drug Interactions
 Use caution when administering imatinib with other drugs affected by the cytochrome
P450 enzyme system.
 In addition, St. John’s wort decreases the effectiveness of many of these drugs and
should be avoided.
 When using nilotinib avoid any other drugs that are known to prolong the QT interval

MISCELLANEOUS ANTINEOPLASTICS
- Many other agents that do not fi t into one of the previously discussed groups are used as
antineoplastics to cause cell death.
- These drugs are used for treating a wide variety of cancers. Table 14.7 lists the unclassified
antineoplastic drugs, their indications, and any special considerations associated with the drug.
- Specific information about each drug may be obtained in a nursing drug guide (see Figure 14.4
for sites of action of the miscellaneous antineoplastic agents).