Medical Oncology Drugs

Question 1

Cisplatin

Answer 1

Class: Platinum; Alkylating Agent
Metabolites: Yes
Dosage Forms: IV
Half-Life: 20-30 minutes
Metabolism: N/A
Clearance: Renal
Dose Adjustments: Yes (Renal), CrCl <60 (<50 for split dosing)
Cross BBB? No
Emetogenicity: High
Watch For:
Myelosuppression
Hypersensitivity Reactions (usually after 6 cycles; 5-20% incidence; possible cross-reactivity between cisplatin and carboplatin)
Nephrotoxicity: Cisplatin (pre- and post-hydration essential. Aim for UO >100mL/h x 24h. Acutely can occur within 10-14days, chronically after 600-800mg/m2 cumulative dosing) > Carboplatin > Oxaliplatin
Ototoxicity: Cisplatin > Carboplatin/Oxaliplatin
Neurotoxicity:
Acute: Oxaliplatin
Chronic: Cisplatin > Oxaliplatin > Carboplatin
Electrolyte Abnormalities
Risk of Secondary Malignancies
*** Sequencing: Give taxane prior to platinum (“Pay your TAXES first”) to limit myelosuppression and enhance efficacy

Question 2

Carboplatin

Answer 2

Class: Platinum; Alkylating Agent
Metabolites: Platinum complexes
Dosage Forms: IV
Half-Life: 1.5h
Metabolism: N/A
Clearance: Renal
Dose Adjustments: Adjust per CrCl (Calvert equation; Total dose (mg) = Target AUC * (GFR + 25), GFR cap @ 125mL/m per ASCO)
Cross BBB? Yes; low concentrations
Emetogenicity: AUC>=4: High, AUC <4: Moderate
Watch For:
Myelosuppression
Hypersensitivity Reactions (Generally after 7 cycles; 1-44% incidence; cross-reactivity with cisplatin possible)
Nephrotoxicity: Cisplatin > Carboplatin > Oxaliplatin
Ototoxicity: Cisplatin > Carboplatin/Oxaliplatin
Neurotoxicity:
Acute: Oxaliplatin
Chronic: Cisplatin > Oxaliplatin > Carboplatin
Electrolyte Abnormalities
Risk of Secondary Malignancies
*** Sequencing: Give taxane prior to platinum (“Pay your TAXES first”) to limit myelosuppression and enhance efficacy

Question 3

Oxaliplatin

Answer 3

Class: Platinum; Alkylating Agent
Metabolites: Diaminocyclohexane (DACH), platinum complexes
Dosage Forms:
Half-Life: 391h
Metabolism: Plasma
Clearance: Renal (54% within 5 days), Feces (2% within 5 days)
Dose Adjustments: Renal (CrCl < 30 = discontinue)
Cross BBB? No
Emetogenicity: Moderate
Watch For:
Myelosuppression
Hypersensitivity Reactions (Generally after 6 cycles; 10-19% incidence)
Nephrotoxicity: Cisplatin > Carboplatin > Oxaliplatin
Ototoxicity: Cisplatin > Carboplatin/Oxaliplatin
Neurotoxicity:
Acute: Oxaliplatin (occurs within hours, can last 7+ days thereafter. Cold sensitivity)
Chronic: Cisplatin > Oxaliplatin > Carboplatin
Electrolyte Abnormalities
Risk of Secondary Malignancies
*** Sequencing: Give taxane prior to platinum (“Pay your TAXES first”) to limit myelosuppression and enhance efficacy
** Give oxaliplatin prior to 5-FU for synergistic effect (Antagonist in opposite sequence)

Question 4

Temozolomide

Answer 4

Class: Triazene; Alkylating Agent
Metabolites: Activation to reactive compound monomethyl triazenoimidazole-carboxamide (MTIC) required for tumour activity
MOAp: Methylation of DNA at the O6, N7 guanine positions leading to DNA double strand breaks and apoptosis
Dosage Forms: IV & PO
Half-Life: 1.2h
Metabolism: Hydrolysis in plasma
Clearance: Renal, feces
Dose Adjustments: None
Cross BBB? Yes
Emetogenicity:
Watch For:
PCP
Peripheral edema
Skin rash
Hepatotoxicity
Photosensitivity
Flu-like syndrome

Question 5

Ifosfamide

Answer 5

Class: Nitrogen Mustard; Alkylating Agent
Metabolites (via CYP3A4):
Active - Isofosfamide mustard, 4-hydroxyifosfamide
Other: Chloroacetaldehyde & Acrolein
Dosage Form: IV
Half-Life: 7-15h
Metabolism: Hepatic
Clearance: Renal
Cross BBB? Ifosfamide: yes, low. Active metabolites: No
Dose Adjustments: Yes (both)
Emetogenicity: >=2g/m2/dose - High. <2g/m2/dose - Moderate
Watch For:
SIADH with hyponatremia
Nephrotoxicity w/ electrolyte wasting (Fanconi syndrome)
Hemorrhagic cystitis (*mitigate with vigorous hydration, co-administration of mercaptoethane sulfonate -> mesna)
Neurotoxicity (timing 2-48h after infusion, *avoid aprepitant, pretreat albumin, methylene blue to treat)
Cardiotoxicity (acutely)
Pneumonitis

Question 6

Bendamustine

Answer 6

Class: Nitrogen Mustard; Alkylating Agent
Dose Adjustments: Not recommended for use if CrCl < 30 mL/m. Not recommended for use in moderate to severe hepatic impairment (AST/ALT >2.5x ULN and bilirubin >1.5x ULN)
Emetogenicity: Moderate
Watch For:
Myelosuppression
Hypersensitivity Reactions
TLS (Highest risk 1st cycle)
Skin Reactions (Irritant with vesicant-like properties)
Peripheral Edema
Drug-Drug Interactions:
Minor substrates of CYP1A2
P-glycoprotein

Question 7

Cyclophosphamide

Answer 7

Class: Nitrogen Mustard; Alkylating Agent
Metabolites (via CYP3A4):
Active - 4-hydroxycyclophosphamide, phosphoramide mustard
Other: Acrolein
Half-Life: 7h
Metabolism: Hepatic
Clearance: Renal
Cross BBB? Yes, including metabolites
Dose Adjustments: Yes (renal), caution (hepatic)
Emetogenicity: >1500mg/m2 - High. <=1500mg/m2 - Moderate
Watch For:
SIADH with hyponatremia
Nephrotoxicity w/ electrolyte wasting (Fanconi syndrome)
Hemorrhagic cystitis (*mitigate with vigorous hydration, co-administration of mercaptoethane sulfonate -> mesna)
Cardiotoxicity (high-dose)
Pneumonitis

Question 8

Melphalan

Answer 8

Class: Nitrogen Mustard; Alkylating Agent
Dosage Forms: PO & IV
Metabolites: None active
Half-Life:
Metabolism: Rapid hydrolysis in plasma
Clearance: Renal (25-30%) & Feces (50%)
Dose Adjustments: Consider with CrCl <50ml/m
Cross BBB? Limited (plasma to CNS ratio 10:1)
Emetogenicity: IV >=140mg/2 = high, <140mg/m2 = moderate; PO is minimal to low
Watch For:
Myelosuppression
Hypersensitivity Reactions
Secondary malignancies
Hepatic sinusoidal obstruction syndrome
Pulmonary toxicity - interstitial pneumonitis

Question 9

Dacarbazine

Answer 9

Class: Triazene; Alkylating Agent
Metabolites: Activation to reactive compound monomethyl triazenoimidazole-carboxamide (MTIC) required for tumour activity
MOAp: Methylation of DNA at the O6, N7 guanine positions leading to DNA double strand breaks and apoptosis
Dosage Forms: IV
Half-Life: 0.5 to 3.5h
Metabolism: Hepatic
Clearance: Renal
Dose Adjustments: Yes (renal)
Cross BBB? <15%
Emetogenicity: High
Watch For:
PCP (prophylax with concomitant RT)
Myelosuppression
Teratogenicity
Hepatic Necrosis
Cutaneous Hypersensitivity
Photosensitivity
Hepatotoxicity
Flu-like syndrome

Question 10

Alkylating Agents

Answer 10

Mechanism of Action: Covalently bonds highly reactive molecules (amines, oxygen, or phosphates) on DNA thus altering DNA structure and function & interfering with DNA base pairing, replication, & transcription
Class Effects:
Dose-Limiting Toxicities-
- Myelosuppression (Neutropenia nadir 6-10 days, recovery 14 - 21 days)
- Nausea, Vomiting, Mucositis, Neurotoxicity, Alopecia
Long Term Toxicities-
- Teratogenic
- Infertility
- Secondary Malignancies

Question 11

Chlorambucil

Answer 11

Class: Nitrogen Mustard; Alkylating Agent

Question 12

Antimetabolites

Answer 12

Includes:
Cytidine Analogs-
Azacitidine
Decitabine
Cytarabine
Gemcitabine
Pyrimidine Analogues -
Fluorouracil
Capecitabine
Trifluridine &
Tipiracil
Purine Analogues -
Cladribine
Clofarabine
Fludarabine
Mercaptopurine
Nelarabine
Pentostatin
Thioguanine
Folate Antagonists -
Methotrexate
Pemetrexed
Pralatrexate

Question 13

Gemcitabine

Answer 13

Class: Cytidine Analog; Antimetabolite
MOA: S Phase. Inhibits DNA synthesis & repair by inhibiting DNA polymerase and ribonucleotide reductase by mimicking cytidine
Metabolites: Yes
Dosage Forms: IV
Half-Life: 32 - 94m (<70m infusion), 245 - 638m (>70m infusion)
Metabolism: Hepatic
Clearance: Renal (lower in elderly patients and women)
Dose Adjustments: Hepatic (Caution if bilirubin >1.2x ULN), Renal (Caution; no specific dose recommendations)
Cross BBB? Unknown
Emetogenicity: Low
Watch For:
Myelosuppression (DLT)
Rash (incl. radiation recall)
Infusion reactions (irritation/burning during infusion)
Flu-like syndrome (pyrexia, arthralgia, headache, chills)
LFT elevations
Pneumonitis (Permanent DC)
HUS (Permanent DC)

Question 14

Fluorouracil

Answer 14

Class: Pyrimidine Analogue; Antimetabolite
MOA: Inhibition of thymidylate synthase. Incorporation into DNA, RNA
Metabolites: FdUMP, FdUTP, FUTP
Dosage Forms: IV
Half-Life: 6-20 minutes; dose-dependent
Metabolism: Hepatic
Clearance: Renal, hepatic
Dose Adjustments: Hepatic
Cross BBB? Yes
Emetogenicity: Low
Watch For:
DPD Deficiency
Myelosuppression
GI Tox - Diarrhea, mucositis (DLT)
Palmar-plantar erythrodysesthesia - DLT
Cardiotoxicity
Radiosensitizer
5-FU Bolus vs. CIV
Bolus: myelosuppression
CIV: PPE, diarrhea, mucositis

Question 15

Capecitabine

Answer 15

Class: Pyrimidine Analogue; Antimetabolite
MOA: Inhibition of thymidylate synthase. Incorporation into DNA, RNA
Metabolites: Capecitabine is a prodrug of 5-FU, converted to 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP) in the liver and tumours
Dosage Forms: PO
Half-Life:
Metabolism: Hepatic
Clearance: Renal
Dose Adjustments: Renal (Dose reduce <50ml/min, discontinue <=30mL/min
Cross BBB? Unknown
Emetogenicity: Low-minimal
Watch For:
DPD Deficiency
Myelosuppression
GI Tox - Diarrhea, mucositis (DLT)
PPE - DLT
Photosensitivity
Cardiotoxicity
Radiosensitizer
Hepatotoxicity

Question 16

Trifluridine & Tipiracil

Answer 16

Class: Pyrimidine Analogue; Antimetabolite
MOA: Incorporated into DNA, interfering with synthesis and cell proliferation. Trifluridine = nucleoside analogue, tipiracil = thymidine phosphorylase inhibitor which prevents metabolism of trifluridine
Metabolites: Yes (inactive)
Dosage Forms: PO
Half-Life: Trifluridine (2h), Tipiracil (2.4h)
Metabolism: Unknown
Clearance: Renal, Fecal
Dose Adjustments: Renal CrCl <=30, Hepatic (Bili > 1.5x ULN = not recommended)
Cross BBB? Unknown
Emetogenicity: Moderate-High
Watch For:
Myelosuppression
Diarrhea
Fatigue
Anorexia

Question 17

Methotrexate

Answer 17

Class: Folate Antagonist; Antimetabolute
MOA: Competitively inhibits dihydrofolate reductase (DHFR). Inhibits conversion of folic acid to tetrahydrofolate, a cofactor for DNA synthesis, repair, and cellular replication
Metabolites: Polyglutamates (active) 7-hydroxy-methotrexate (inactive)
Dosage Forms: IV or PO
Dosing: Low dose: <=50mg/m2 IV or PO, Moderate: 50-500mg/m2 IV, High Dose: >=500mg/m2 IV (MUST HAVE LEUCOVORIN RESCUE)
Half-Life: 3-10h (low dose, <30mg/m2), 8-15h (high dose)
Metabolism: Hepatic
Clearance: Clearance
Dose Adjustments: Renal (dose reduce CrCl <=80) Hepatic (dose reduce bili 2.5-4x ULN, discontinue >4x ULN)
Cross BBB? Poorly
Emetogenicity: Moderate (IV doses >=250mg/m2), Low (IV doses >30 and <250mg/m2), Minimal (IV doses <= 30mg/m2 or PO doses)
Watch For:
AKI (via intratubular crystallization, prevent using vigorous hydration with alkalinized IV fluids)
Hepatotoxicity (transient transaminitis, hyperbilirubinemia; resolves within 5-7 days following clearance of serum)
Mucositis (directly related to duration of exposure)
Myelosuppression (directly related to duration of exposure; DLT with leukopenia, thrombocytopenia)

Question 18

Methotrexate (Supportive Care)

Answer 18

Hydration:
- Aggressive IV hydration ensures adequate renal perfusion and drug clearance
- 100-200ml/m2 starting 12h prior to MTX and continued until MTX <0.1uM

Urinary Alkalinization
- MTX and metabolites POORLY SOLUBLE in acidic pH
- Maintaining urinary pH >=7 increases MTX solubility 5-8 fold
- Sodium bicarbonate 50-150mEq/L at 125-250mL/h
- Acetazolamide 250-500mg q6-8h

Drug Monitoring
- Extent of cytotoxicity is dependent on concentration and duration of cellular exposure to MTX
- Goal levels depend upon protocol and method of MTX administration

Leucovorin Rescue
- Exogenous source of reduced folate to help rescue normal cells
- Started 24h following MTX administration, continue until MTX <0.1uM
- Dose depends on protocol (ex. 50mg loading dose then 15mg q6h and titrated according to MTX concentration)

Drug-Drug Interactions
- Avoid NSAIDs, Sulfonamides, Antifolates, Penicillins, Proton pump inhibitors, Fluoroquinolones, and Probenacid

Glucarpidase
- Recombinant carboxypeptidase enzyme approved for the treatment of toxic MTX levels in patients with delayed clearance due to impaired renal function
- MTX levels are unreliable for at least 48h after glucarpidase administration

Question 19

Pemetrexed

Answer 19

Class: Folate Antagonist; Antimetabolites
MOA: Inhibits DNA synthesis by inhibiting purine and thymidine nucleotide and protein synthesis
Metabolites: Yes
Dosage Forms: IV
Half-Life: 3.5h
Metabolism: No Data
Clearance: Renal
Dose Adjustments: Renal (Not recommended CrCl<45)
Cross BBB? Unknown
Emetogenicity: Low
Watch For:
Myelosuppression - DLT
Rash and cutaneous reactions
Nephrotoxicity
Stomatitis
Interstitial pneumonitis (treat with steroids, permanently DC pemetrexed)
Supportive Care:
Rash - Pretreat dex 4mg PO BID x 3 days starting day prior to pemetrexed
Myelosuppression and mucositis/stomatitis - Vitamin supplementation with folic acid 400-100mcg PO daily and B12 1000mcg IM q9w (begin both 1 week prior to initiation, continue for 3 weeks after last dose of pemetrexed). Consider Sulcrate of viscous lidocaine to treat mucositis.

Question 20

Microtubule Inhibitors

Answer 20

Includes:
Taxanes -
Cabazitaxel
Docetaxel
Paclitaxel
Nab-paclitaxel

Vinca Alkaloids -
Vinblastine
Vincristine
Vinorelbine

Miscellaneous -
Ixabepilone
Eribulin

Mechanism of Action:
M Phase
Taxanes - Microbutuble stabilizers. Promote microtubule assembly, stabilizes existing microtubules, and inhibits microtubule disassembly
Vinca Alkaloids - Microtubule destabilizers. Bind specifically to beta-tubulin and block polymerization with alpha tubulin to form microtubules

Question 21

Paclitaxel

Answer 21

Class: Microtubule Inhibitors
Metabolites: Hydroxylated metabolites (inactivated)
Dosage Forms: IV
Half-Life: 9.9h
Metabolism: Hepatic
Clearance: Hepatic
Dose Adjustments: Hepatic (starting with AST/ALT >2x ULN)
Cross BBB? No
Emetogenicity: Low
Extravasation Potential: Irritant
Watch For:
Myelosuppression (DLT, Docetaxel > Paclitaxel)
Hypersensitivity reactions (risk 31-45%, can be due to paclitaxel or vehicle cremophor, pre-medicate Dex 20mg, diphenhydramine 25-50mg, H2RA)
Peripheral neuropathy (Paclitaxel > Docetaxel)
Extravasation
Alopecia
Onycholysis/nail bed changes

Question 22

Docetaxel

Answer 22

Class: Microtubule Inhibitor
Metabolites: None active.
Dosage Forms: IV
Half-Life: 11h
Metabolism: Hepatic
Clearance: Hepatic
Dose Adjustments: Hepatic (discontinue with ANY increase in bilirubin, OR >1.5x AST/ALT)
Cross BBB? No
Emetogenicity: Low
Extravasation Potential: Irritant
Watch For:
Myelosuppression (DLT, Docetaxel > Paclitaxel)
Hypersensitivity reactions (risk 6-21%, can be due to Docetaxel or vehicle polysorbate 80, pre-medicate Dex 8mg PO BID x 3 days beginning one day prior to docetaxel OR 20mg once prior to dose)
Peripheral neuropathy (Paclitaxel > Docetaxel)
Extravasation
Alopecia
Onycholysis/nail bed changes
Fluid retention

Question 23

Cabazitaxel

Answer 23

Class: Microtubule Inhibitor
Metabolites: Yes
Dosage Forms: IV
Half-Life: 95h
Metabolism: Hepatic (CYP3A4)
Clearance: Fecal
Dose Adjustments: Hepatic (TBili >1.5x ULN reduce, stop >3X ULN)
Cross BBB? Yes
Emetogenicity: Low
Extravasation Potential: Irritant
Watch For:
Myelosuppression (DLT)
Hypersensitivity reactions (pre-medicate Dex 8mg, diphenhydramine 25, H2RA)
Peripheral neuropathy
Extravasation
Alopecia
Onycholysis/nail bed changes
Diarrhea
Cystitis

Question 24

Nab-Paclitaxel

Answer 24

Class: Microtubule Inhibitor
Metabolites: Yes
Dosage Forms: IV
Half-Life: 13-27h
Metabolism: Hepatic (CYP2C8 major, minor CYP3A4)
Clearance: Feces, Urine
Dose Adjustments: Hepatic (Discontinue Bili >5X ULN or AST >10x ULN)
Cross BBB? Unknown
Emetogenicity: Low
Extravasation Potential: Irritant
Watch For:
Myelosuppression (DLT)
Hypersensitivity reactions (much lower risk, no need to pre-medicate)
Peripheral neuropathy (nab-paclitaxel > paclitaxel)
Extravasation
Alopecia
Onycholysis/nail bed changes
Diarrhea
Cystitis

Question 25

Eribulin

Answer 25

Class: Microtubule Inhibitor MOAp: Inhibits formation of mitotic spindles causing mitotic blockage -> works on G2/M phase Metabolites: Trace inactive Dosage Forms: Half-Life: 40h Metabolism: Minimally metabolized. P-gp substrate Clearance: Dose Adjustments: CPA - Dose 1.1mg/m2, CPB - 0.7mg/m2, CPC - discontinue. Caution CrCl <50mL/min (dose 1.1mg/m2) Cross BBB? Unknown Emetogenicity: Low Extravasation Potential: Minimal Watch For: Myelosuppression - neutropenia DLT Peripheral neuropathy - DLT QTc Prolongation Elevated AST/ALT Electrolyte Abnormalities

Question 26

Topoisomerase Inhibitors

Answer 26

Includes: Topoisomerase I - Irinotecan Topotecan Sacituzumab Govitecan Trastuzumab Deruxtecan Topoisomerase II - Daunorubicin Doxorubicin Epirubicin Idarubicin Epidophyllotoxins - Etoposide Mechanism of Action: - Binds to topoisomerase & stabilize the cleavable complex. Causes single or double-stranded DNA breaks that result in cell death Class Effects: Myelosuppression Extravasation Emetogenicity High - Moderate: Etoposide (PO) Moderate: Irinotecan (conventional) Low: Irinotecan (liposomal) Etoposide (IV) Topotecan (IV & PO)

Question 27

Irinotecan

Answer 27

Class: Topoisomerase I inhibitor Metabolites: Metabolized to SN38 in the presence of hepatic or gastrointestinal carboxylesterase. Metabolized in part by CYP3A4 and UGT1A1 to inactive metabolites Dosage Forms: IV Half-Life: 5.8 - 11.7h (irinotecan); 7.7-17h (SN38) Metabolism: Hepatic Clearance: Hepatic, renal Dose Adjustments: Hepatic (AST/ALT >3X ULN, Bilirubin >35); consider for patients homozygous for the UGT1A1*28 allele Cross BBB? Unknown Emetogenicity: Moderate Extravasation Potential: None Watch For: Myelosuppression - DLT Diarrhea - DLT, Irinotecan >>> Topotecan (Be aware of cholinergic syndrome as cause for early diarrhea, atropine 0.25-1mg IV or SC as treatment) Alopecia ILD (start steroids, permanent DC) Increased transaminases

Question 28

Topotecan

Answer 28

Class: Topoisomerase I Inhibitor Metabolites: Lactone form, n-desmethyl metabolite (Active) Dosage Forms: PO or IV Half-Life: 2-3h (IV) Metabolism: Hepatic Clearance: Renal Dose Adjustments: Renal (Adjust CrCl < 30 IV, <50 PO) Cross BBB? Yes Emetogenicity: Low Extravasation Potential: Minimal Watch For: Myelosuppression - DLT Diarrhea - DLT, Irinotecan >>> Topotecan Alopecia ILD (start steroids, permanent DC) Increased transaminases Flu-like symptoms

Question 29

Sacituzumab Govitecan

Answer 29

Class: Antibody drug conjugate; topoisomerase I inhibitor MOAp: Binds to Trop-2-expressing cells and is internalized with subsequent release of SN-38 via hydrolysis of the linker Metabolites: N/A Dosage Forms: IV Half-Life: 23.4h Metabolism: SN-38 metabolized via UGT1A1 Clearance: Unknown Dose Adjustments: None Cross BBB? No Emetogenicity: Two-Three drug anti-emetic regimen (Dex + 5-HT3 or NK1RA) Extravasation Potential: Watch For: Neutropenia (particularly for UGT1A1*28 allele patients) Diarrhea (may develop cholinergic diarrhea syndrome as well, consider atropine) Infusion Reactions (H1/H2 blockers, antipyretics, and possibly corticosteroids as pre-medication)

Question 30

Doxorubicin

Answer 30

Class: Anthracycline; topoisomerase II inhibitor MOAp: In addition to Topo II inhibition, intercalate into DNA, directly affecting transcription and replication. Metabolized in the liver to form oxygen free radicals. Metabolites: Doxorubicinol Dosage Forms: IV Half-Life: 20-48h Metabolism: Hepatic Clearance: Hepatic Dose Adjustments: Hepatic (Reduce dose if Bili >ULN) Cross BBB? No Emetogenicity: Moderate (<60mg/m2), High (>=60mg/m2) Extravasation Potential: Vesicant Watch For: Lifetime Dose (450-500mg/m2) Myelosuppression - DLT Cardiomyopathy - Acute -> pump failure within first 2-3 days as arrhythmia and/or conduction system problems, pericarditis and/or myocarditis Chronic -> dose-dependent, dilated cardiomyopathy (baseline LVEF and regular monitoring required) Secondary Malignancies Mucositis Alopecia Rash Red-coloured urine (may last 1-2 days) Radiation recall Hyperpigmentation

Question 31

Epirubicin

Answer 31

Class: Anthracycline; topoisomerase II inhibitor Metabolites: Yes Dosage Forms: IV Half-Life: 30-40h Metabolism: Hepatic Clearance: Hepatic Dose Adjustments: Hepatic (50% dose if elevated Bili, AST 2-4x ULN) Cross BBB? No Emetogenicity: High (>90mg/m2), Moderate (<= 90mg/m2) Extravasation Potential: Vesicant Watch For: Lifetime dose 900mg/m2 Myelosuppression - DLT Cardiomyopathy - Acute -> pump failure within first 2-3 days as arrhythmia and/or conduction system problems, pericarditis and/or myocarditis Chronic -> dose-dependent, dilated cardiomyopathy (baseline LVEF and regular monitoring required) Secondary Malignancies Mucositis Alopecia Rash

Question 32

Etoposide

Answer 32

Class: Epidophyllotoxin; Topoisomerase II inhibitor Metabolites: Metabolized cyp450 system (CYP3A4 involved) Dosage Forms: PO or IV Half-Life: 11h (IV), 6.8h (PO) Metabolism: Hepatic Clearance: Renal, hepatic Dose Adjustments: Renal adjustment CrCl <50 mL/min Cross BBB? Trace Emetogenicity: Low Extravasation Potential: Irritant Watch For: Myelosuppression - DLT Mucositis Alopecia Hypersensitivity Secondary Malignancy (MDS/AML 2-3years after exposure, due to 11q23. Risk higher after 2g/m2 cumulative exposure)

Question 33

Bleomycin

Answer 33

Class: Antibiotic MOA: Directly binds to DNA generating free radicals and causing single and double strand breaks Metabolites: Yes Dosage Forms: Half-Life: 2-5h (IV bolus), 9h (continous IV infusion) Metabolism: Hepatic, gut Clearance: Renal Dose Adjustments: Adjust CrCl <50mL/min Cross BBB? No Emetogenicity: Minimal Extravasation Potential: None Watch For: Pulmonary toxicity Hepatotoxicity Idiosyncratic reactions Dermatologic Toxicity (hyperpigmentation) ***Risk Factors for Pulmonary Toxicity Age > 70years Cumulative dose > 400 units Poor Renal Function Prior Radiation Concurrent Oxygen Smoking G-CSF Use (data from lymphoma) Concomitant pulmonary toxic medications/chemotherapy