Oncology Study Guide

Winter 2023

PHARMACY CALCULATIONS: Will only need to calculate dosing parameter once on exam. Will be
given dosing parameters for the other 2 cases

● What will you be provided on the exam?

• Table of normal lab values (adult and pediatric)
• Table of emetogenicity level of common chemotherapy drugs

● What you will NOT be provided but need to know:

• Any of the equations on in this document for estimating the correct dosing weight, correct
dosing BSA or CrCL in both adult and pediatric patients.
IBW
- male: 50kg + 2.3kg (inches over 5 ft)
- female: 45kg + 2.3kg (inches over 5 ft)
- no need to calculate if <12 yr old or <45kg, use actual BW
- will be <12 yo on exam
- >45kg but less than 5 ft →IBW will be 45kg or 50kg
BSA

BSA adult = 0.00784 * (weight in kg)^0.425 * (height in cm)^0.725

● round to the tenth for this class

● use BWadj if actual BW is > 1.3IBW
○ BWadj = IBW + 0.4(actual - IBW)
● use actual BW if BW < 1.3IBW or IBW

𝑤𝑒𝑖𝑔ℎ𝑡 (𝑘𝑔) * ℎ𝑒𝑖𝑔ℎ𝑡 (𝑐𝑚)]

BSA pediatrics (Mosteller) =
3600

CrCL
(140 −𝑎𝑔𝑒) * 𝑤𝑒𝑖𝑔ℎ𝑡 (𝑘𝑔)
CrCL = * 0. 85 𝑖𝑓 𝑓𝑒𝑚𝑎𝑙𝑒
72 * 𝑆𝐶𝑟

Exceptions:

- Carboplatin use actual body weight for Calvert eqn

- Capped at 125ml/min
- Obese pt: if actual BW >1.3IBW, use BWadj
- All capped at 120ml/min except carboplatin

𝑘 * ℎ𝑒𝑖𝑔ℎ𝑡 (𝑐𝑚)
CrCL pediatrics = where k = 0.413
𝑆𝐶𝑟

• Any of the equations pertaining to calculations, including metric equivalents and household measures.
1 kg = 2.2 lbs
2.54 cm = 1 in

1
 units for BSA in m2
1 teaspoon = 5mL
1 tablespoon = 15mL
1 fl oz = 30mL
1mL = 15 drops

LECTURE TITLE: MECHANISMS OF ONCOGENESIS

Session Objectives:

• Be able to describe the general structure of DNA.

• Understand the general process of normal DNA repair.
- caretaker genes protect against DNA damage
- encode DNA repair proteins
- ensure integrity of genome
- LOF → accumulation of mutations → genetic instability
• Be able to describe and explain the 3 primary mechanisms of DNA damage that can lead to cancer.
• If damage to DNA occurs, be able to describe the five main processes cells will use to try to repair the
damage.
- base excision repair
- mismatch repair
- insertion/deletion of single base pair mismatch
- nucleotide excision repair
- bulky DNA damage from radiation and chemical mutagens
- homologous recombination repair - ds breaks
- error prone -reattaching broken strands
- use homologous chromosome as template to fill gap
- defects →predisposition to cancer: increased rate of chromosome rearrangements,
mutations, genomic instability, higher dependence on NHEJ for ds repairs
- non-homologous end joining - ds breaks
- defects → predisposition to cancer: sensitive to radiation, translocations, general
genomic instablity
• Understand the role of BRCA1 and BRCA2 in the role of breast cancer.
- BRCA1 is a HRR gene
- interaction with other proteins
• Provide an example of mismatch repair disorder.
- lynch syndrome
• Provide an example of homologous recombinant repair.
- familal breast cancer
• Describe the function of telomeres.
- length safeguards against uncontrolled cell proliferation
• Describe the most common type of epigenetic mutation.
- DNA methylation
- silences gene expression without changing DNA sequence or affecting base pairing
- inheriable
- potentially reversible
• Describe what translocation is and how it related to the development of chronic myelogenous leukemia.

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 - rearrangements of chromosome → can turn on oncogene. turn tumor suppressor gene off
(insertion or deletion) → philadelphia chromosome → chimeric BCR-ABL → CML
• Define oncogene.
- gene with potential to cause cancer
- mutations
• Define tumor repressor gene.
- “breaks”regulates cell division
- if not functioning → cell divides uncontrollably

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LECTURE TITLE: CELL CYCLE SPECIFIC AGENTS

Session Objectives:

● Be able to provide three reasons, along with examples, for designing multi-drug regimens to treat
cancer.
● Table 1- Different categories of anti-tumor agents. For each of the different classes of drugs be
able to provide:
a. Mechanism of action
b. Important drug-class related toxicities
● Table 2- Individual drugs and specific drug-related toxicities. For each of the individual drugs be
able to provide:
a. Mechanism of action
b. Important drug-specific toxicities
c. YOU DO NOT NEED TO KNOW DOSES FOR DRUGS LISTED IN TABLE 2.

● Be able describe VOD, the primary organs affected, and agents we used to prevent or treat VOD.
○ associated with cyclophosphamide and busulfan used at highest doses
○ chemo-induced damage to the liver - lining of blood vessels
○ damaged sinusoidal endothelium sloughs and obstructs liver → injury to hepatocytes → if
severe: renal and respiratory failure
○ occurs within first 1-2 wks post conditioning, up to 1-20% pt
○ s/sx
■ weight gain
■ ascites
■ tender hepatomegaly
■ pulmonary infiltrates
■ hyperbilirubinemia
■ congestive heart failure
a. You are responsible for knowing dose, route, frequency of defibrotide.
● 6.25mg/kg IV over 2 hr every 6h for 21 days
○ reassess and continue if sx indicate ongoing txt
● ppx in high risk pt undergoing HCT or txt upon VOD diagnosis
● can increase risk of bleeding
b. What are the criteria for diagnosis of VOD?
● seattle criteria: development of 2 of the following within 20 days of transplant
○ hyperbilirubinemia (>2 mg/dL) can cause hepatic damage if T bili is ~40-50s
○ tender hepatomegaly
○ weight gain

● For this class you should be recommending a dose reduction to prevent toxicity for all medications that
undergo renal elimination AND the estimated GFR is less than 70ml/min.
Definition for the different levels of renal impairment:
○ Definition for the different levels of renal impairment:
○ Normal renal function > 70ml/min
○ Mild renal impairment 50-69ml/min
○ Moderate renal impairment 30-49ml/min
○ Severe renal impairment 29ml/min or below
● For this class you should be recommending a dose reduction to prevent toxicity for a medications that under
a high first pass metabolism in the liver AND the total bilirubin is elevated above the normal range.

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 • Be able to provide appropriate dose modifications for individual drugs in the setting of renal or hepatic
impairment.
MTX renal
- rescue with folic acid
- trough level of MTX at 48h if > 0.1 uM → rescue with lucovorin

• Be able to describe the clinical implications for genetic variants of TPMT.

- normal = *1/*1 homozygous WT
- TPMT *2 or *3
- reduced ability to clear inactive metabolite → hepatotoxicity
• Provide appropriate dose modifications, if given the TPMT genotype of a patient.
- 6MP dose reduction needed! typically 90% but just show dose reduction
- heterozyg: start with reduced doses (30-70%) and adjust on desired myelo
- homo variant: start with 10-fold (90%) reduction twice weekly
- consider alt therapy if non malignant
• Be able to describe the impact of UGT1A1 variants (*28) on irinotecan metabolism and drug-related
toxicity.
- extra TA repeats in promoter region → reduced expression of UGT1A1 → low level of
glucuronidation → increased risk of neutropenia and diarrhea
• Be able to describe doxorubicin-induced cardiomyopathy.
- free radicals that interferes with DNA synthesis→ apoptosis of cells → tissue damage →
cardiotoxicity
- lifetime limits

• Be able to calculate the life-time cumulative dose of doxorubicin and understand the risks associated
with exposure plus/minus radiation.
- <550 mg/m2 or <400mg/m2 with radiation
- radiation can cause tissue damage to heart → additive effect
• What are some therapeutic options (drug class, name only) can be useful for treating vinca alkaloid or
taxane-induced neuropathy?
- duloxetine (anti-depressant) or gabapentin (Gabapentinoids)

TABLE 1- DIFFERENT CATEGORIES OF ANTI-TUMOR AGENTS.

Drug Category Mechanism of Action Key Toxicities

Contain reactive groups that bind to DNA or
RNA therefore inhibiting synthesis.
Severe myelosuppression
Crosslinking can occur within or between Gonadal toxicity
Alkylators strands of DNA
Secondary tumors
Guanine is the most common nucleic base
targeted.

Structural analogues of endogenous

molecules require for DNA and RNA
Anti-Metabolites synthesis. Incorporation into cellular pathways Severe myelosuppression
results in disruption of DNA and RNA
synthesis.

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Topoisomerase Inhibitors
Cause breaks in DNA by
disrupting the function of topoisomerase
enzymes, which are responsible for
maintaining the correct structure of DNA
(coiling and uncoiling). Severe myelosuppression
Topo I- single strand breaks

Topo II-double strand breaks

Inhibit cell mitosis by interfering with
Taxanes microtubule formation or function- prevents Severe myelosuppression
microtubule disassembly

Vinca Alkaloids Inhibit cell mitosis by interfering with

microtubule formation or function- prevent Severe myelosuppression
microtubule assembly

Estrogen Antagonists
Aromatase Inhibitors
Hot flashes
Partial estrogen antagonist
Bone pain
Prevents the final step in the conversion of
androgens to estrogen in peripheral tissues Bone pain

Luteinizing Hormone Chronic use leads to downregulation of the

Releasing Hormones LHRH receptors, leading to decrease QTc prolongation
Agonists testosterone in men

TABLE 2- INDIVIDUAL DRUGS AND SPECIFIC DRUG-RELATED TOXICITIES.

Individual Drug Category of Drug Key Toxicities

Mucositis
VOD
Busulfan Alkylator (nitrogen mustard)
Neurotoxicity
Pulmonary Toxicity
Melphalan Alkylator (nitrogen mustard) VOD
Cardiotoxicity
Cyclophosphamide Alkylator (nitrogen mustard) VOD
Hemorrhagic cystitis
Thiotepa Alkylator (nitrogen mustard) VOD
Ifosfomide Alkylator (nitrogen mustard) Myelosuppression
Pulmonary toxicity with cumulative
Carmustine Alkylator (nitrosourea) doses >
1400mg/m2
Lomustine Alkylator (nitrosourea) Nephrotoxicity
Nephrotoxicity
Ototoxicity
Cisplatin Alkylator (platinum)
High emetogenicity
Neuropathy
Nephrotoxicity
Carboplatin Alkylator (platinum) Much better toxicity profile as
compared to cisplatin
Temozolomide Alkylator (triazine) Myelosuppression
Myelosuppression Hepatoxicity
Dacarbazine Alkylator (triazine)

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Bleomycin Alkylator-like (Glycopeptide antibiotic) Pulmonary Toxicity

Fludarabine Anti-Metabolite (purine analogue)- inhibits de novo Neurotoxicity

purine synthesis
Clofarabine Anti-Metabolite (purine analogue)- inhibits de novo Skin toxicity (rash)
purine synthesis Transient increases in LFTs
6-mercatopurine Anti-Metabolite (purine analogue)- inhibits de novo Liver damage
purine synthesis
Cytarabine Anti-Metabolite (pyrimidine analogue)- competes with Skin toxicity (rash)
dCTP to inhibit DNA synthesis.
Gemcitabine Anti-Metabolite (pyrimidine analogue)- competes with Skin toxicity (rash)
dCTP to inhibit DNA synthesis.
5-flurouracil Anti-metabolite (pyrimidine analogue)- inhibition of Severe diarrhea
thymidylate synthase and incorporation of metabolites
into DNA and RNA
Methotrexate Anti-metabolite (folate pathway)- inhibition of Nephrotoxicity
dihydrofolate reductase
Folic acid effector molecule- Active metabolite of folic n/a
Leucovorin acid required for nucleic acid synthesis.

MTX: rescue healthy cells from MTX toxicity

5-FU: enhances the toxicity of 5-FU by inhibiting

thymidylate synthase. Thus lower doses of 5-FU can be
administered
Pemetrexed Anti-metabolite (folate pathway)- inhibition of purine Mucositis
and pyrimidine synthesis. It inhibits 3 enzymes:
thymidylate synthase, dihydrofolate reductase and
glycinamide ribonucleotide formyltransferase.

Irinotecan Topoisomerase I inhibitor Severe diarrhea associated with

UGT1A1*28

Topotecan Topoisomerase I inhibitor Myelosuppression

Daunorubicin, Topoisomerase II inhibitor (Anthracycline) Cardiotoxicity:
Doxorubicin Lifetime < 550mg/m2 or <
400mg/m2 (if received radiation)

Etoposide Topoisomerase II inhibitor Myelosuppression

Mitoxantrone Topoisomerase II inhibitor Myelosuppression
Docetaxel Taxane Myelosuppression
Paclitaxel Taxane Peripheral neuropathy
Vinblastine Vinca Alkaloid Myelosuppression
Vincristine Vinca Alkaloid Hypersensitivity reactions
Peripheral neuropathy
Vinorelbine Vinca Alkaloid Myelosuppression
Tamoxifen Partial estrogen antagonist Bone pain Hot
flashes
Anastrozole Aromatase Inhibitor, inhibits aromatase preventing the Bone pain
conversion of androgens to estrogens

Letrozole Aromatase Inhibitor, inhibits aromatase preventing the Bone pain

conversion of androgens to estrogens

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Goserelin Temporary disease flare with
Luteinizing Hormone Releasing Hormones Agonists- initiation of treatment- increase in
preventing the generation of testosterone serum testosterone QTc
prolongation

Leuprolide Luteinizing Hormone Releasing Hormones Temporary disease flare with

Agonists-preventing the generation of initiation of treatment- increase in
testosterone serum testosterone QTc
prolongation

SMALL MOLECULE INHIBITORS

Session Objectives:
• Be able to describe the function of a protein kinase.
- regulate cell growth and proliferation
- activate signal transduction pathways → DNA regulation, protein synthesis, cell cycle regulation,
cell proliferation
• Be able to describe how protein kinases work in association with major signal transduction pathways.
- stream of downstream signals
• Be able to explain why protein kinases are considered “druggable” therapeutic targets.
- has pocket for drug to target
- easy to make ATP mimetics
- usually, mutations to kinases are activating → easier to make drugs to turn off activating protein
than to turn on an inactivating protein
• Be able to explain the role of translocation in the development of CML.
- philadelphia chromosome → chimeric BCR-ABL kinase that is always turned on → signals
cancer cell growth and proliferation

• Be able to describe what the Philadelphia chromosome is and its role in the development of cancer.
- chromosome 9 and chromosome 22 break and exchange portions → creates an abnormally
small chromosome 22 and a new combination of instructions for your cells that can lead to the
development of chronic myelogenous leukemia.
• Be able to recommend a drug effective at inhibiting BCR-ABL and describe how it works.
imatinib - inhibits BCR-ABL by binding competitively → preventing the kinase from signaling cancer cells
growth and proliferation

MONOCLONAL ANTIBODIES
You are NOT responsible for knowing dose, route, frequency for the monoclonal antibodies and check point
inhibitors discussed in this lecture.
• Describe the mechanism of action for a monoclonal antibody.
• Describe the mechanism of action for a monoclonal antibody-conjugate.
definition: mAb that links with a small molecule cytotoxic agent → extracellular targeting of mAb with
intracellular effect of small molecule inhibitor → more targeted delivery of cytotoxic agents
MOA: ADC travel in plasma → selectively bind to cellular targets→ ADC-receptor complex internalized →
cytotoxic agent gets released → apoptosis

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 • Describe the mechanism of action for a checkpoint inhibitor and describe the role of T cell immunity in
this process.
T cell activation by antigen recognition
• Provide correct pre-medications orders for the prevention of hyper-sensitivity infusion related reactions
by individual drug.
• You are responsible for providing drug, dose, route, and frequency for premedication including:
- Diphenhydramine- IV/PO 25-50mg IVx1 30-60min prior to start
- Acetaminophen-IV/PO 500-1000 mg PO x1 “ ”
- Corticosteroids-IV/PO dexa 12mg PO/IV x1 30-60min prior
• You are responsible for providing drug, dose, route, and frequency for treatment of infusion related
reactions including:
o Hydrocortisone-IV 100mg IV push, may repeat 50mg IV q6h prn sx
o Epinephrine-IV 0.3mg IM repeat as needed
o Diphenhydramine-IV 50mg IV push, may repeat 50mg IV q6h prn sx
• Be able to list the binding target (mechanism of action), important consideration for preparing the
medication, key side-effects, and appropriate supportive care for each of the monoclonal antibodies and
check point inhibitors discussed.
rituximab: SQ and solution vials not interchangeable, don’t shake or dilute with other drugs

daratumumab: SQ and solution vials not interchangeable, admin w micron filter, protect from light, don’t shake
gemtuzumab: protect from light, over 2 hr through 0.2 micron inline filter, don't shake, vials need to be RT
before reconstituting
inotuzumab: protect from light, don’t shake, each vial reconstitute with 4ml sterile water to 0.25mg/ml, add
required volume to NS to total 50ml

Brentuxima:protect from light,

mABs to know
Drug Drug Target Premedications Key side-effects specific
to this agent

Rituximab Binds to CD20 on B-cells, leading APAP, Diphenhydramine, =/- Tumor lysis syndrome
to apoptosis steroid

Daratumumab Binds to CD-38 on myeloma APAP, Diphenhydramine, Steroid Zoster reactivation

cells, leading to apoptosis May consider H2 blocker

Gemtuzumab Binds to CD-33 on leukemic APAP, Diphenhydramine, Steroid Tumor lysis syndrome
cells, leading to apoptosis QTc prolongation
VOD

Inotuzumab Binds to CD-22 on malignant B APAP, Diphenhydramine, Steroid QTc prolongation

cells, leading to apoptosis VOD

Brentuximab Binds to CD-30 on lymphoma APAP, Diphenhydramine, =/- Peripheral Neuropathy

cells, leading to apoptosis steroid

CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING AND MUCOSITIS

● The list for emetogenicity of chemotherapy agents will be provide during the exam.
● Be able to identify risk factors for increased risk of CINV.
9
 female
younger than 50
little to no alcohol use
prior use of chemotherapy
● Be able to define and classify the type of CINV for acute, delayed, anticipatory, breakthrough, and
refractory.
● Be able to define by percentage what is high-risk, moderate, low, and minimal risk for level of
emetogenicity.
minimal-low: acute
moderate-high: acute and delayed
● Be able to recommend an appropriate treatment regimen by level (minimal to high) and/or type of CINV
(acute, delayed, anticipatory, breakthrough, and refractory) including drug class, drug, dose, route, and
frequency.
Be able to identify risk factors for mucositis.
Be able provide non-pharmacologic and pharmacologic recommendations for prevention N/V and mucositis.

● When providing an anti-emetic regimen, you must be able to provide drug, dose, route, and
frequency for:
○ 5HT3 antagonist- ondansetron IV/PO
○ NK-1 Antagonist- aprepitant IV/PO
○ Corticosteroids- dexamethasone IV/PO
○ Atypical Antipsychotic- olanzapine PO
○ Benzodiazepine- lorazepam IV/PO

SUPPORTIVE CARE 1- TLS AND HYPERCALCEMIA

Tumor Lysis Syndrome (TLS)
• Describe the pathophysiology of TLS.
tumor lyse spontaneously or to chemo → release of intracellular components cause electrolyte
abnormalities → onc emergency!! → organ complication or death
- increase uric acid, potassium, phosphate
• Describe and identify risk factors for TLS.
tumor type: cancer of blood, large b cell lymphoma, leukemia, burkitt’s lymphoma, wbc ~10
cancer mass: bone marrow involvement, bulky or extensive metastasis, organ infiltration, renal
infiltration/obstruction
cell lysis potential: high rate of prolif, sensitivity to anticancer therapy, intensity of initial anticancer therapy
patient:
- baseline uric acid > 7.5 mg/dl
- nephropathy before diagnosis
- acidic urine
- hypotension
- dehydration or volume depletion

• Be able to recognize laboratory parameters and symptoms of TLS. 12-72 hr after chemo
> 2 abnormal metabolic lab or metabolic lab changed 25% from baseline normal abnormal

uric acid → uric acid crystals obstructive uropathy 1.5 - 7 >= 8 mg/dl
- flank pain (lower back)
oliguira (lowered urine output)
-AKI

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 K 3.5 - 5 > 6 mEq
- N/V/D
muscle weakness, cramps
EKG abnormalities, arrhythmias, SOB

phos 2.8 - 4.5 > 6.5mg/dl

- N/V/D, lethargy, muscle cramps/spasms

Ca -HYPO 8.6 - 10.3 <= 7 mg/dl

- confusion, delirium, muscle cramps/spasms, arrhythmias

• Be able to positively diagnose patients with TLS based on laboratory parameters.

clinical TLS: lab TLS + at least 1 significant complication;
● cardiac arrhythmias
● seizures
● renal insufficiency ( Scr 0.3 mg/dl, > 1.5xULN, or decreased urine output > 0.5ml/kg/hr x 6hr)

• Be able to identify and describe the potential complications of untreated TLS.

renal failure, cardiac arrhythmias, seizures, neuromuscular instability

Discuss commonly used pharmacologic agents managing hyperuricemia and electrolyte abnormalities in
TLS, specifically:
1. Hydration- including dose, route, frequency
a. NS 2-3 L/m2 IV daily
2. Allopurinol- including dose, route, frequency, important toxicities, and laboratory parameters for
monitoring.
a. 300mg/m2 daily or 10mg/kg daily in 3 divided doses q8h
i. max 800 mg/day
ii. ADE: GI irritation, rash, hypersensitivity
iii. DDI: azathioprine, 6MP - toxic metabolite accumulation → myelo
iv. monitor: uric acid levels, ADE, renal fxn (give 50% dose for CrCL <30)
v. Give 1-2 days before chemo, continue for 10-14 after or until uric acid stable
3. Rasburicase- including dose, route, frequency, important toxicities, and laboratory parameters
for monitoring.
a. 3mg or 6mg IV x1, 4 hours to effect
b. ADE: NVD, rash, anaphylaxis
c. monitor: uric acid levels, ADE, caution in G6PD deficiency (hemolytic anemia)
d. mainly treatment because $$$
other
- hyperkalemia
- ca gluconate 1000mg IV over 2-5 min (if EKG abnormal or arrhythmias)
- stabilize and antag K effect on myocardium
- insulin R 10U + 50% dextrose 25g/50ml + albuterol 10-20mg neb over 10 mins
- shift K from extracellular to intracellular space
- remove K
- furosemide 20-40mg IV with hydration
- na polystyrene sulfate (SPS) 15-60g po q6h, avoid in bowel obstruction
- dialysis only if life threatening/renal failure
- decrease K intake
- hold agents that potentiate hyperK: acei/arb, spirno, bactrim, K supp, TPN/tube feed
- hyperphosphatemia
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 - decrease phos intake: diet, promote hydration
- decreases GI absorption
- oral phosphate binders
- avoid aluminum in CKD
- remove serum phosphate: in severe case → dialysis
- hypocalcemia
- usually corrects on its own
- risk of ca phos precipitation
- if symptomatic: ca gluconate 1000mg slow IV infusion , no faster than 200mg/min
- monitor EKG
• Given a patient case, identify signs and symptoms of TLS and recommend an appropriate treatment
plan including appropriate monitoring parameters and follow-up.

Hypercalcemia:
• Describe the pathophysiology of hypercalcemia of malignancy.
1. 80% Production of PTHrP (parathyroid hormone related protein) →increae bone resorption and
decrease renal elimination of calcium
2. vitamin D
3. 20% cytokine factors → osteolysis → increase clast, decrease blast activity

• Describe and identify risk factors for hypercalcemia.

• Be able to recognize laboratory parameters and symptoms of hypercalcemia of malignancy.

normal 8.6-10.3 mg/dl
mild: 10.5-11.9
moderate: 12-13.9
severe: >= 14

corrected eqn: Ca + 0.8(4 - albumin)

• Be able to positively diagnose patients with hypercalcemia of malignancy based on laboratory
parameters.
• Be able to identify and describe the potential complications of untreated hypercalcemia
bone metastases
renal: kidney stones, dehydration, renail failure, constipation
GI: abdominal pain
neurological: altered mental status, lethargy, coma
CV: shortened QT intervals, arrhythmias
• Be able to describe when to choose the use of bisphosphonates or calcitonin as therapy and be able to
describe the mechanism of action.

hydration: NS 1-2L bolus followed by 150-300 ml/hr maintenance to restore intravascular volume and promote
renal excretion of Ca
diuresis: furosemide 20-40mg IV q12-24 hr to increase renal excretion and block ca reabsorption in LoH
- given with hydration, avoid thiazide

zoledronic acid 4mg IV over 15-20 min or pamidronate 60-90mg IV over 2 hr

- inhibit osteoclasts and decrease ca release from bones
- ADE: bone pain, decrease ca, K, PO4, mg; transient flu like sx, ONJ
- monitor: electrolytes, SCr
- reserve after fluids and diuretics
- renal dose adjustment

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 - Scr =< 4.5mg/dl - standard dose, no adj
- >4.5mg/dl - discussion, can extend infusion to 30-60min
- hemodialysis - 3mg IVx 1 from one case report

calcitonin 4-8 IU/kg SQ or IV q8-12 hr

- PTH antagonist → inhibit activity of osteoclast to block bone resorption
- quicker onset: 2hr
- ADE: rhinitis, flushing
- can only use up to 48 hr due to tachyphylaxis (downregulation of calcitonin receptor → resistance, and
decrease efficacy) → rebound hypercalcemia if given >72hr

• Given a patient case, identify signs and symptoms of hypercalcemia and recommend an appropriate
treatment plan including appropriate monitoring parameters.
decrease intake/absorption of ca: TPN, suppl, thiazide diuretics, antacids, vit d suppl, lithium

SUPPORTIVE CARE 2- GROWTH FACTORS

• Be able to define neutropenia. decrease in circulating neutrophils

NCCN: ANC<500 or <1000 with expected decrease to <= 500 within 48h
- severe: ANC <100
- units: cells/mm3 or 1.5*10^9 cells/L
• Describe the negative outcomes associated with prolonged neutropenia.
risk for life-threatening infections (bacterial, fungal, viral), febrile neutropenia
• Be able to calculate an absolute neutrophil count (ANC).
o You will not be provided the calculation for this estimation on the exam.
o (%seg + %bands)/100 *total WBC
• seg - increase when bone marrow want to pump out more cells (not mature yet)
• band - increase when pt is trending towards infection
• Compare and contrast different colony-stimulating factors used for the prophylaxis or treatment of
neutropenia (G-CSF and GM-CSF):
G-CSF GM-CSF

indication prophylaxis and treatment treatment

MOA bind to CSF receptor to promote production, maturation, and activation

of myeloid cells

t1/2 filgrastim (short): 3-4 hr 2.7h

- tbo-fig only prophylaxis
pegfilgrastim (long): 15-80hr
- prophylaxis only

freq of admin short: daily for 14 day or ANC rec daily until ANC recovery

long: once per cycle

SE bone pain, flu-like sx, chest pain

more ADE with GM CSF

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 monitoring ANC

• Compare and contrast different options for treatment of cancer-related anemia.

- cancer associated: underlying comorbidities, tumor infiltration of BM, chronic blood loss at tumor
site
- chemotherapy associated: impaired hematopoiesis in BM, cumulative myelo, decreased
production of EPO due to nephrotoxicity
• Compare and contrast different erythropoietin-stimulating factors used for the treatment of ca
cancer-related anemia (epoetin alfa vs darbepoetin). o Indication for use o half-life
o frequency of administration o route of administration
o side effects o monitoring parameters

epoetin alfa darbepoetin

indication palliative chemo and Hgb <10 and anticipated chemo >=2 mo

route SQ

t1/2 16-67hr 35-139 hr

freq of admin 150 unit/kg SQ 3x week 2.25mcg/kg SQ once weekly →

- if hgb doesn’t increase by
>= 1g/dl and remains <10
after 4 wk → increase to
300 units/kg TIW
or
40,000 unit SQ once weekly
- titrate up to 60k units
4.5mcg/kg wk if “ “
or
500mcg SQ q3wk until chemo
completion
reduced dose by 40% if hgb
increases >1g/dl in any 2 wk
period or hgb normal level

SE HTN, edema, headache, arthralgias, fatigue

baseline ferritin >100mcg/L, serum transferrin sat >20%
monitoring
Hgb, Hct, BP

• Be able to identify adverse drug reactions associated with erythropoietin-stimulating factors, along with
contraindications for treatment.

• You must be able to provide drug, dose, route, and frequency of:
● filgrastim
- 5mcg/kg IV daily for 14 day or ANC recovery >500
- at least 24 hr before or after chemo
- round to nearest vial size 300 or 480mcg
● peg-filgrastim
- 6 mg SQ x1 per cycle
- 24 h after chemo and at least 14 day before next cycle
● sargramostim
- 250 mcg/m2 SQ or IV daily until ANC recovery
- start 24 hr after last chemo
- round to nearest vial size 250mcg

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IMMUNOSUPPRESSANTS- PHARMACOLOGY AND PHARMACOKINETIC PROPERTIES

• Be able to describe the difference between allogeneic and autologous HCT.

allogeneic: someone else’s stem cells
- eliminate abnormal hematopoietic cells, then
replace them in nonmalignant dx
- rescue from myeloablative therapy
- graft vs leukemia (attack on host cells) or graft
vs tumor effect (GVT)
autologous: patient’s own stem cells
- can do dose intensification of chemo or
radiation (con: high tox from chemo)
- myeloablation leading to death without
hematopoietic stem cell rescue!!!

- Define myeloablative and be able to explain how this is different from reduced-intensity conditioning.

myeloablative reduced intensity conditioning

- high dose chemo (typically with CY), to
kill all stem cells (healthy and cancer)
- very toxic!! → need to pick healthy pt’s
- young, limited comorb
- need stem cell infusion to recover host
immune system (hematopoietic cell
rescue
- won’t completely ablate pt’s stem cells
- lower doses/ less intensity allowing its use in
older pt or those with comorbidities
- “mixed chimerism” want host % to be larger than
recipient
- donor cell will eventually take over
recipient stem cell
- relying on GVT to get rid of residual dx
- donor cell recognize malignant cells as
foreign and attack

- both have risk of graft vs host disease (GVHD)

• Be able to describe the purpose of post-transplant immunosuppression.

- given to allogeneic HCT patients prevent GVHD
- acute within 100 day post transplant
- chronic > 100 days
- commonly impacted: skin, GI, liver
- inhibit and minimize activity of donor T cell
- combo therapy can:
- provide effective immunosuppression
- allow for lower doses of each drug to limit tox
- minimize overlapping tox
• Be able to provide the mechanism of action for cyclosporin/tacrolimus, mycophenolate, sirolimus,
methotrexate, and ATG. see table
- T cell depletion in blood and peripheral lymphoid tissues through complement-dependent lysis
and Tcell activation and apoptosis
• Be able to provide key pharmacokinetic properties of cyclosporin/tacrolimus, mycophenolate, sirolimus,
methotrexate, and ATG.
TAC
- 99% protein binding
- t1/2 =8-12hr, <1% excreted unchanged in urine
- not dialyzable
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 - extensive CYP3A4, P-gp
- dose adjust for renal and hepatic insufficiency
- hepatic cleared but it somehow affects the kidneys too (vasoconstricts the afferent
arterioles and decreases GFR)
- black pt require higher doses than caucasians to achieve similar trough
- <12 yr need higher doses to achieve similar trough

MMF
- rapid and extensive absorption, F= 94%
- 97% plasma protein binding (mainly albumin)
- metabolism to MPA, enterohepatic cycling
- t1/2 =16-19 hr , inactive 87% excreted in urine
- dose adjust for renal and hepatic insufficiency

Sirolimus
- oral solution F=14%, tablet F=18%
- t1/2 =62 hr, fecal excretion 98%
- shorter t1/2 in peds ~14-22hr
- 92% plasma protein binding (mainly albumin)
- extensive CYP3A4, P-gp
- dose adjust for hepatic only

MTX
- rapid but unpredictable absorption
- 50% protein bound, 3-10% plasma enter CSF
- slowly penetrates 3rd space fluids (fluid overload, ascites)
- t1/2 = 3-10 hr low dose used for HCT
- dose adjustment for renal and hepatic impairment
- liver metabolism, renal excretion

ATG
- no oral bioavailabilty
- Vd = 0.12L/kg
- not metablized
- t1/2 = 2-3 days

• Be able to identify important side-effects of cyclosporin/tacrolimus, mycophenolate, sirolimus,

methotrexate, and ATG. see table
SIR - monitor fasting lipid profile (metabolic SE)

• Be able to provide special considerations for preparing cyclosporin/tacrolimus, mycophenolate,

sirolimus, methotrexate, and ATG.
TAC
- non PVC bag and tubing
- give with or without food CONSISTENTLY
- separate doses 10-12hr apart (6am,6pm inpatient)
Sirolimus
- loading: 3x the desired maintenance dose
- give with or without food CONSISTENTLY
MMF
- IV with D5W over at least 2 hr

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 - PO on empty stomach
MTX
- day +1 dose must be given at least 24 hr after end of stem cell infusion
- MD/NP/PharmD must approve for all doses (3rd spacing)
- mucositis risk for high risk pt → leucovorin rescue from MTX tox: 5-10mg IV q6h x 4-6 doses, at
least 12 hr after MTX dose
ATG
- infuse over at least 6 hours, can be extended if symptoms occur (fever, chills)

• Be able to identify key drug or food interactions for cyclosporin/tacrolimus, mycophenolate, sirolimus,
methotrexate, and ATG.
TAC - CYP3A4
- increase levels: azoles, macrolide, venetoclax, Paxlovid
- decrease levels: rifabutin, rifampin, sirolimus, methylprednisolone
- avoid GFJ, seville orange, pomelo, (pomegranate, black mulberry, wild grape)
MMF
- decrease bioavailability→ separate dose by 2 hr from mg suppl, phosphate binders, antacids
Sirolimus
- increase levels: azoles, macrolide, venetoclax, Paxlovid
- decrease levels: rifabutin, rifampin, methylprednisolone
- avoid GFJ, seville orange, pomelo, (pomegranate, black mulberry, wild grape)
MTX
- increase levels: NSAIDs, sulfonylureas, omeprazole, pantoprazole, phenytoin, SMZ/TMP
ATG - none :)

• Be able to appropriately dose immunosuppression in the setting of organ dysfunction, drug-drug

interactions, and comorbidities.
TAC CYP3A4
- vorconazole and posaconazole - STRONG CYP3A4 inhibitor
- initiation → dose decrease TAC by 50-67%
- fluconazole and isavuconazole
- decrease TAC by 25%
- dose decrease TAC by ⅓ when switching azoles
- phenytoin, rifampin, rifabutin - monitor more frequently, may need to increase TAC
- methylprednisolone: may inhibit initially then induce TAC metab → monitor TAC during taper
Sirolimus CYP3A4
- azoles
- CI: voriconazole and posaconazole but can be done with vigilant monitoring
- fluconazole and isavuconazole - mild to moderate inhibitors of CYP3A4
- increase SIR levels
- monitor freq unti stable and if azole is stopped
- phenytoin, rifampin, rifabutin - monitor more frequently, may need to increase SIR
MMF
- 30-50% dose reduction for hepatic impairment

• Be able to safely convert a patient from oral to IV immunosuppression.

TAC
- IV: PO 1:3 or 4 (absolute bioavailability =20%)
MMF: 1:1 conversion

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 • Be able to adjust immunosuppression based on individual goal ranges provided for MMF, SIR, TAC.
desired dose = ( Css desired/ Css current) * current dose

TAC 5-15ng/ml; >20ng/ml = toxic

trough: wait at least 24-36 hr after starting/adjustment for steady state
- oral: draw immediately prior to dose
- IV: anytime
50% dose reduction if Scr 2x baseline, hold if SCr>2 mg/dl

SIR 5-15 ng/mL, QD dosing

trough: immediately prior to dose
- wait 3-4 days after loading
- wait 7-14 days between dose adj for maintenance dose
30% reduction for mild-mod hepatic impairment
50% reduction for severe hepatic impairment

MMF 15mg/kg IV or PO BID-TID (acutal BW) -> 250mg cap vs 500mg tab, or 200mg/ml solution
- max 1g per dose
GFR <25ml/min : don’t exceed 1g BID

MPA: 1-3.5 microg/mL

- 50% reduction if CrCL<30ml/min
- 50% reduction if Tbili >10mg/dL

CSA 200-400ng/mL (0-3 months), 100-200ng/mL (3+ months )

cyclosporine - 50% dose reduction if Scr 2x baseline, hold if SCr>2 mg/dl

• Be able to provide any special considerations needed for the preparation, infusion, and premedication
of ATG.

Immunosuppressants
Drug Mechanism of action Most common side-effects
Inhibits calcineurin thereby inhibiting Nephrotoxicity
Cyclosporine (SOT T-cell function and activation Magnesium wasting
lecture) Neurotoxicity
HTN
Inhibits calcineurin thereby inhibiting Nephrotoxicity
T-cell function and activation Magnesium wasting
tacrolimus
Neurotoxicity
HTN
Inhibition of mTOR thereby inhibiting Hypertriglycerides
sirolimus the function of both B and T cells. Hypertension
Inhibit inosine monophosphate thereby GI (nausea/diarrhea)
mycophenolate inhibiting T-and B-cell function and Myelosuppression
activation
rATG Binds to multiple T-cell specific antigens Infusion Reactions Requires
(antithymocyte leading to cell death Premedication: acetaminophen,
globulin)

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 diphenhydramine, and +/-
dexamethasone
anti-metabolite via folate pathway - Nephrotoxicity
MTX
inhibition of dihydrofolate reductase
primarily work on CD4+ cells → Elevated blood glucose
inhibition of pro-inflammatory cytokines Weight gain
Steroids and activation of anti-inflammatory Hypertension
pathways Bone loss

SOLID ORGAN TRANSPLANT (SOT)

NOTE: many of these overlap with the immunosuppression lecture so please review those slides for content.

• Be able to describe the general pathophysiology of how organ rejection occurs.

- recipients immune system recognizing and responding to allograft
- allorecognition process (graft rejection)
- T cell recognizes unprocessed allogeneic MHC molecule on graft APCs OR processed
peptide of allogeneic MHC bound to self MHC molecule on host APC
• Identify the timeline for different types of rejection.
• Be able to provide the mechanism of action for cyclosporin/tacrolimus, mycophenolate, sirolimus,
methotrexate, and corticosteroids.
• Be able to provide key pharmacokinetic properties of cyclosporin/tacrolimus, mycophenolate, sirolimus,
methotrexate, and corticosteroids.
• Be able to identify important side-effects of cyclosporin/tacrolimus, mycophenolate, sirolimus,
methotrexate, and corticosteroids.
• Be able to provide special considerations for preparing cyclosporin/tacrolimus, mycophenolate,
sirolimus, methotrexate, and corticosteroids.
• Be able to identify key drug or food interactions for cyclosporin/tacrolimus, mycophenolate, sirolimus,
methotrexate, and corticosteroids.
• Be able to appropriately dose immunosuppression in the setting of organ dysfunction, drug-drug
interactions, and comorbidities.
• Be able to safely convert a patient from oral to IV immunosuppression.
• Be able to adjust immunosuppression based on individual goal ranges provided for MMF, SIR, and
TAC.
• Be able to provide any special considerations needed for the preparation, infusion, and premedication
of ATG.

DRUG INTERACTIONS
• Be able to identify key drug interactions focused on chemotherapy and immunosuppression.
CYP450 induction: takes 14 days ~90% enzyme recovery after inducer cessation
antifungals - CYP3A4
- fluconazole: moderate, reversible inhibitor
- voriconazole: strong, reversible inhibitor
- caspofungin (IV only): minimal/no DDI
tyrosine kinase inhibitors - CYP3A4
- imatinib: moderate, reversible inhibitor
- dasatinib: strong, reversible inhibitor

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 antidepressants
- paroxetine: strong 2D6 inhibitor
- fluoxetine: strong 2C19, 2D6 inhibitor
- bupropion: strong 2D6 inhibitor
- minimal/no DDI:
- citalopram, escitalopram, venlafaxine, mirtazapine
steroids
- high dose → CYP3A4 induction
- physiologic dose 1-1.5 mg/m2/day prednisone
Cyclophosphamide (CY), Thiotepa, Busulfan
- CYP3A4
- inhibitor: voriconazole, fluvoxamine (mod)
- inducer: CBZ, st john’s wort
- 2B6
- inhibitor: voriconazole, clopidogrel
- inducer: CBZ, rifampin (mod)
- 2C9
- inhibitor: fluconazole (mod), fluvoxamine
- inducer: aprepitant
- APAP → deplete glutathione → caution if liver is jeopardized
• Be able to discontinue or offer alternatives to offending agents in an appropriate timeline based on key
pharmacokinetic properties of a drug.
- stop unnecessary meds, OTC, suppl
- competitive inhibitors ~5-7 t1/2, inducers ~14 days
- if possible, transition to less offensive alternative
• Be able to describe very common interactions as enzyme inhibition, enzyme induction, transporter
inhibition, or pharmacodynamic, along with examples.

supportive care - common culprits

aprepitant/fosaprepitant
- inhibit 34A (moderate)
- induce 2C9 weak
5HT3RA, olanzapine for CINV → QTc prolongation

QTc prolongation
- fluroroquinolone abx: levofloxacin, cipro, moxifloxacin
- macrolide abx: clarithromycin, erythromycin
- azoles
- antipsychotic
- methadone, sumatriptan, antiarrhythmic agents

BREAST CANCER
Be able to describe the incidence of breast cancer.
○
● Be able to describe the etiology of breast cancer.
● Identify risk factors of breast cancer.

early menarche
○ late menopause

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 ○ female
○ increasing age
○ ethnicity: african americans, whites
○ genetic mutations
● Describe the methods for diagnosing and staging breast cancer.
● Be able to define neoadjuvant vs adjuvant therapy.
● Be able to describe the possible reasons for management including surgery, radiation, chemotherapy,
hormone therapy, and targeted therapy.
● Be able to provide the “preferred” chemotherapeutic regimens for HER-2 negative and HER-2 positive
disease.
● Be able to provide supportive care for drug-induced neutropenia in the setting of breast cancer therapy.
● Be able to provide appropriate endocrine therapy for treatment of breast cancer based on menopausal
status, including SERM, aromatase inhibitors, and LHRH agonists.
● Be able to provide targeted therapy when indicated by genomic markers for HER-2 or ER status.
● For each of the drugs discussed be able to describe key dosing considerations for dose selection,
frequency, key toxicities, labs to monitor both before and during therapy.
●
Breast Cancer Agents

Drug Mechanism of Action Key Drug-Specific Toxicities

Palbociclib CD Kinase inhibitors- Inhibits cyclin-dependent Myelosuppression

Ribociclib kinase (CDK4 and 6), preventing progression Hepatotoxicity (ribociclib, abemaciclib)
Abemaciclib from G1 to S cell cycle phase
Ribociclib: … QTc prolongation and
thromboembolism

Tamoxifen Partial estrogen antagonist Bone pain

Hot flashes

Anastrozole Aromatase Inhibitor, inhibits aromatase

preventing the conversion of androgens to Bone pain
estrogens

Letrozole Aromatase Inhibitor, inhibits aromatase

preventing the conversion of androgens to Bone pain
estrogens

Goserelin Luteinizing Hormone Releasing Hormones Temporary disease flare with initiation of
Agonists- preventing the generation of treatment- increase in serum testosterone
testosterone QTc prolongation

Leuprolide Luteinizing Hormone Releasing Hormones Temporary disease flare with initiation of
Agonists-preventing the generation of treatment- increase in serum testosterone
testosterone QTc prolongation

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Trastuzumab Infusion reaction
Binds to extracellular domain of HER2 leading Cardiomyopathy: avoid concurrent use with
to antibody-dependent cellular cytotoxicity anthracycline
Pulmonary toxicity

LUNG CANCER
Don’t need to select select combo chemo unless asked about targeted therapy
No supportive care for skin

• Be able to describe the incidence of lung cancer.

- slightly higher in men
- women>men in non smoker
- black men >white
- >= 65+, median 70
• Be able to describe the etiology of lung cancer.
• Identify risk factors of lung cancer.
- smoking 85-90% cases
- quitting - after 10-15 yr risk decreases by 50%
- asbestos, radon, chemicals
- chest radiation
- family hx of lung cancer
• Describe the methods for diagnosing and staging lung cancer (T-N-M-S).
- tumor (size, location)
- nodes (regional, distant)
- metastases (yes or no)
- stage: IV most severe, metastatic = palliative
• Define and describe the incidence of SCLC and non-SCLC.
o won’t be tested on SCLC

• Be able to distinguish between localized vs generalized signs/symptoms.

• Be able to describe the possible reasons for management: surgery, radiation, chemotherapy.
- radiation: shrink tumor so it can be ressected
- chemo: residual dx, or unresectable
• Be able to explain the use of alkylator based systemic therapy.
- form intra and interstrand crosslinks in DNA to break →interfere with DNA fxn and synthesis →
so cancer can’t proliferalte
• Be able to explain the use of immunotherapy including check point inhibitors.
- allow T cell to stay active to attack cancer cells
• Be able to explain the use of targeted therapy such as EGFR, KRAS, ALK, MET, ROS, B-Raf, Ret and
NTRK.
• For each of the drugs discussed be able to describe key dosing considerations for dose selection,
frequency, key toxicities, labs to monitor both before and during therapy.

Lung Cancer Agents

Drug Drug Class Mechanism of Action Key side-effects specific to this agent

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Pembrolizumab PD-1 inhibitor Binds to PD-1 receptor on T-cells, Hepatotoxicity
thus promoting anti-tumor T-cell Pneumonitis
effects Thyroid disfunction
Rash
Diarrhea
*Avoid with concomitant use of steroids

Nivolumab PD-1 inhibitor Binds to PD-1 receptor on T-cells, Hepatotoxicity

thus promoting anti-tumor T-cell Pneumonitis
effects Thyroid disfunction
Rash
Diarrhea
*Avoid with concomitant use of steroids

Osimertinib EGFR Binds to EGFR, to block kinase Rash

activated pathways Diarrhea

Sotorasib KRAS Binds to EGFR, to block kinase Diarrhea

activated pathways Musculoskeletal pain
Hepatoxicity

Lorlatinib ALK Binds to EGFR, to block kinase Hypertriglyceridemia

activated pathways Mood changes

Table 3- List of drugs and doses you must commit to memory!

Drug Indication Instructions

(Adult dosing)
Acetaminophen Premedication- hypersensitivity 500-1000mg PO x 1, 30-60 min prior to start of
reactions mAb infusion.
Aprepitant Prevention of CINV Day 1- 130mg IV x 1, 30-60 min
prior to start of chemotherapy

Days 2 and 3- 80mg IV/PO x 1, 30-60 min prior

to start of chemotherapy.

Allopurinol Prevention of TLS 10mg/kg/day divided in three doses. Max

800mg/day.

Begin PO 24-48 hours prior to start of

chemotherapy.

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Defibrotide Prophylaxis or Treatment of VOD 6.25mg/kg IV over 2 hours every
6 hours for 21 days

At 21 days reassess and continue if symptoms

indicted ongoing treatment is required.

Diphenhydramine Premedication- hypersensitivity 25-50mg IV x 1, 30-60 min prior to start of mAb

reactions infusion.
Diphenhydramine Treatment for infusion-related 50mg IV x 1, administer immediately by IV
reactions push. May repeat 50mg IV Q6H prn
symptoms of reaction.

Dexamethasone Premedication- hypersensitivity 8-12mg IV PO x 1, 30-60 min prior to start of

reactions mAb infusion.
Dexamethasone Prevention of CINV Day 1: 8-12mg IV x 1, 30-60 min prior to start
of chemotherapy

If indicated:
Days 2-4: 8-12mg IV x 1, 30-60
min prior to start of chemotherapy

Epinephrine Treatment for infusion-related 0.3mg IM x 1, repeat as needed.

reactions (anaphylaxis)
Hydrocortisone Treatment for infusion-related 100mg IV x 1, administer immediately by IV
reactions push. May repeat 50mg IV Q6H prn symptoms
of reaction.

Lorazepam Treatment of breakthrough CINV 0.5-1mg PO Q6H prn N/V

Normal Saline Hydration for TLS 2-3 L/m2 IV daily
Mesna Prevention of hemorrhagic cystitis Dose equivalent to cyclophosphamide.
with high dose cyclophosphamide

Strategy 1- Total dose can be infused over 24

hours, beginning 1-2 hours prior to first dose of
CY and continue for 24 hours after the end of
CY.

Strategy 2- Total dose is divided into 4 doses:

On each day of CY give 15min prior to first
dose, then 4 and 8 hours post CY infusion.

24
Olanzapine Prevention of CINV (acute/delayed) Days 1: 5-10mg PO x 1, 30-60 min prior to start
of chemotherapy

If indicated:
Days 2-4: 5-10mg PO x 1, 30-60 min prior to
start of chemotherapy

Olanzapine Treatment for breakthrough CINV 5-10mg PO once daily PRN N/V

Ondansetron Prevention of CINV Day 1: 8mg IV x 1, 30-60min prior to start of

chemotherapy.

If indicated:
Days 2-4: 8mg IV x 1, 30-60min prior to start of
chemotherapy.
Ondansetron Treatment for breakthrough CINV 4-8mg PO Q8H prn CINV
Rasburicase Prevention or treatment of TLS 3-6 mg IV over 30min x 1, May repeat every
24 hours as indicated by labs (max 5 doses).

Filgrastim Treatment/prevention of 5mcg/kg SQ or IV once daily 24 hours after last

neutropenia chemotherapy as
indicated per protocol for prevention or
treatment of
neutropenia

Peg-filgrastim Prevention of neutropenia 6mg SC x 1 per cycle.

Administer 24 hours after last chemotherapy
and > 14 days before next cycle.

Sargramostim Treatment of neutropenia (2nd line) 250mcg/m2 SC or IV once daily 24 hours after
last chemotherapy as indicated per protocol for
prevention or treatment of
neutropenia

Table 5- Medications that must be dose reduce for organ dysfunction.

Drug Primary Site of Primary Route of Dose Modifications for
Metabolism Clearance Organ Dysfunction

Cyclosporine Liver Bile Hepatic Impairment

Feces Renal Dysfunction

Tacrolimus Liver Bile Hepatic Impairment

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 Feces Renal Dysfunction

Sirolimus Liver Bile Hepatic Impairment

Feces

MMF Liver Renal Hepatic Impairment

Renal Dysfunction

MTX n/a Renal Renal Dysfunction

Busulfan Liver Bile Hepatic Impairment

Feces

Cyclophosphamide Liver Liver (primary) Hepatic Impairment

Renal (limited) Renal Dysfunction (if
severe)

Carboplatin n/a Renal Renal Dysfunction

Fludarabine n/a Renal Renal Dysfunction

Clofarabine n/a Renal Renal Dysfunction

6-MP n/a n/a Hepatic Impairment

26