Chapter 081. Principles of Cancer Treatment (Part 11)

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Table 81-2 Commonly Used Cancer Chemotherapy Agents Drug Exam ples of Usual Doses Toxicity Issues Interactions, Direct DNA-Interacting Agents Alkylators Cyclophospha 2000 400– mg/m2 Marrow (relative Liver metabolism required mide IV platelet sparing) to activate to phosphoramide 100 mg/m2 PO qd Common alkylatora Mesna protects Cardiac dose) against Cystitis mustard + acrolein (high "high-dose" bladder damage Mechloretha mine 6 mg/m2 IV day Marrow Topical use in cutaneous lymphoma Vesicant 1 and day 8 Nausea Chlorambucil 1–3 mg/m2 qd PO Marrow Common alkylatora Melphalan 8 mg/m2 qd x 5, nadir) PO Marrow (delayed Decreased renal function delays clearance GI (high dose) Carmustine (BCNU) 200 mg/m2 IV nadir) Marrow (delayed 150 mg/m2 PO dose) GI, liver (high Renal Lomustine (CCNU) 300 PO 100– mg/m2 nadir) Marrow (delayed Ifosfamide 1.2 g/m2 per day e qd x 5 + Myelosuppressiv Isomeric...

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Chapter 081. Principles of Cancer Treatment (Part 11) Table 81-2 Commonly Used Cancer Chemotherapy Agents Drug Exam Toxicity Interactions, ples of Usual Issues Doses Direct DNA-Interacting Agents Alkylators Cyclophospha 400– Marrow (relative Liver 2000 mg/m2 metabolism required
mide IV platelet sparing) to activate to phosphoramide 100 Cystitis mustard + acrolein mg/m2 PO qd Common Mesna alkylatora protects against Cardiac (high "high-dose" bladder dose) damage Mechloretha 6 Marrow Topical use in mine mg/m2 IV day cutaneous lymphoma Vesicant 1 and day 8 Nausea Chlorambucil 1–3 Marrow mg/m2 qd PO Common alkylatora Melphalan 8 Marrow (delayed Decreased mg/m2 qd x 5, nadir) renal function delays PO clearance
GI (high dose) Carmustine 200 Marrow (delayed (BCNU) mg/m2 IV nadir) 150 GI, liver (high mg/m2 PO dose) Renal Lomustine 100– Marrow (delayed (CCNU) 300 mg/m2 nadir) PO Ifosfamide 1.2 Myelosuppressiv Isomeric g/m2 per day e analogue of qd x 5 + cyclophosphamide Bladder mesna More lipid Neurologic soluble Metabolic Greater acidosis activity vs testicular
Neuropathy neoplasms and sarcomas Must use mesna Procarbazine 100 Marrow Liver and mg/m2 per tissue metabolism Nausea day qd x14 required Neurologic Disulfiran- Common like effect with alkylatora ethanol Acts as MAOI HBP after tyrosinase-rich foods Dacarbazine 375 Marrow Metabolic (DTIC) mg/m2 IV day activation Nausea 1 and day 15
Flulike Temozolomid 150– Nausea/vomiting Infrequent e 200 mg/m2 qd myelosuppression Headache/fatigue x 5 q28d or 75 mg/m2 qd Constipation x 6–7 weeks Altretamine 260 Nausea Liver (formerly mg/m2 per activation Neurologic hexamethylmelamin day qd x14– (mood swing) Barbiturates e) 21 as 4 enhance/cimetidine divided oral Neuropathy diminishes doses Marrow (less) Cisplatin 20 Nausea Maintain high mg/m2 qd x5 urine flow; osmotic Neuropathy IV 1 q3–4 diuresis, monitor weeks or Auditory intake/output K +, 100–200 Mg2+ Marrow platelets 2 mg/m per
dose IV q3–4 > WBCs Emetogenic— weeks prophylaxis needed 2+ 2+ Renal Mg , Ca Full dose if CrCl > 60 mL/min and tolerate fluid push Carboplatin 365 Marrow platelets Reduce dose mg/m2 IV > WBCs according to CrCl: to q3–4 weeks AUC of 5–7 mg/mL Nausea as adjusted per min [AUC = for CrCl Renal (high dose) dose/(CrCl + 25)] Oxaliplatin 130 Nausea Acute mg/m2 q3 reversible Anemia weeks over 2 neurotoxicity; h or 85 chronic sensory mg/m2 q2 neurotox cumulative weeks with dose; reversible laryngopharyngeal
spasm Antitumor antibiotics Bleomycin 15–25 Pulmonary Inactivate by mg/d qd x5 bleomycin hydrolase Skin effects IV bolus or (decreased in continuous Raynaud's lung/skin) IV Hypersensitivity O2 enhances pulmonary toxicity Cisplatin- induced decrease in CrCl may increase skin/lung toxicity Reduce dose if CrCl < 60 mL/min Actinomycin 10–15 Marrow Radiation µg/kg per day
D qd x5 IV Nausea recall bolus Mucositis Vesicant Alopecia Mitomycin C 6–10 Marrow Treat mg/m2 q6 superficial bladder Vesicant weeks cancers by Hemolytic- intravesical infusion uremic syndrome Delayed Lung marrow toxicity CV—heart Cumulative failure marrow toxicity Etoposide 100– Marrow (WBCs Hepatic (VP16-213) 150 mg/m2 > platelet) metabolism—renal IV qd x3–5d 30% Alopecia or 50 Reduce doses
mg/m2 PO qd Hypotension with renal failure x21d Hypersensitivity Schedule- or up (rapid IV) dependant (5 day to 1500 better than 1 day) Nausea mg/m2 per Late dose (high Mucositis (high leukemogenic dose with dose) stem cell Accentuate support) antimetabolite action Topotecan 20 Marrow Reduce dose mg/m2 IV with renal failure Mucositis q3–4 weeks No liver over 30 min Nausea toxicity or 1.5– Mild alopecia 3 mg/m2 q3–4 weeks over 24 h or 0.5 mg/m2 per
day over 21 days Irinotecan 100– Diarrhea: "early Prodrug (CPT II) 150 mg/m2 onset" with cramping, requires enzymatic IV over 90 flushing, vomiting; "late clearance to active min q3–4 onset" after several drug "SN 38" weeks doses Early diarrhea or 30 Marrow likely due to biliary mg/m2 per excretion Alopecia day over 120 Late diarrhea, h Nausea use "high-dose" Vomiting loperamide (2 mg q2–4 h) Pulmonary Doxorubicin 45–60 Marrow Heparin and daunorubicin mg/m2 dose aggregate; Mucositis q3–4 weeks coadministration Alopecia increases clearance or 10–
30 mg/m2 Cardiovascular Acetaminoph dose q week acute/chronic en, BCNU increase liver toxicity or Vesicant continuous- Radiation infusion recall regimen Idarubicin 10–15 Marrow None mg/m2 IV q 3 established Cardiac (less weeks than doxorubicin) or 10 mg/m2 IV qd x3 Epirubicin 150 Marrow None mg/m2 IV q3 established Cardiac weeks Mitoxantrone 12 Marrow Interacts with mg/m2 qd x3 heparin Cardiac (less
or 12– than doxorubicin) Less alopecia, 14 mg/m2 q3 nausea than Vesicant (mild) weeks doxorubicin Blue urine, Radiation sclerae, nails recall Indirect DNA-Interacting Agents Antimetaboli tes Deoxycoform 4 Nausea Excretes in ycin mg/m2 IV urine Immunosuppressi every other on Reduce dose week for renal failure Neurologic Inhibits Renal adenosine deaminase 6- 75 Marrow Variable
Mercaptopurine mg/m2 PO Liver bioavailability or up Nausea Metabolize by 500 mg/m2 xanthine oxidase PO (high Decrease dose dose) with allopurinol Increased toxicity with thiopurine methyltransferase deficiency 6- 2–3 Marrow Variable Thioguanine mg/kg per bioavailability Liver day for up to Increased 3–4 weeks Nausea toxicity with thiopurine methyltransferase deficiency
Azathioprine 1–5 Marrow Metabolizes mg/kg per to 6MP, therefore Nausea day reduce dose with Liver allopurinol Increased toxicity with thiopurine methyltransferase deficiency 2- 0.09 Marrow Notable use in Chlorodeoxyadenosi mg/kg per hairy cell leukemia Renal ne day qd x7 as continuous Fever infusion Hydroxyurea 20–50 Marrow Decrease dose mg/kg (lean with renal failure Nausea body weight) Augments PO qd Mucositis
or 1–3 Skin changes antimetabolite effect g/d Rare renal, liver, lung, CNS Methotrexate 15–30 Marrow Rescue with mg PO or IM leucovorin Liver/lung qd x3–5 Excreted in Renal tubular or 30 urine mg IV days 1 Mucositis Decrease dose and 8 in renal failure or 1.5– NSAIDs 2 12 g/m per increase renal day (with toxicity leucovorin) 5-Fluorouracil 375 Marrow Toxicity mg/m2 IV qd enhanced by Mucositis x5 leucovorin Neurologic or 600 Dihydropyrim
mg/m2 IV Skin changes idine dehydrogenase days 1 and 8 deficiency increases toxicity Metabolizes in tissues Capecitabine 665 Diarrhea Prodrug of mg/m2 bid 5FU due to Hand-foot continuous; intratumoral syndrome 2 1250 mg/m metabolism bid 2 weeks on/ 1 off; 829 mg/m2 bid 2 weeks on/ 1 off + 60 mg/d leucovorin Cytosine 100 Marrow Enhances arabinoside mg/m2 per activity of alkylating Mucositis day qd x7 by agents continuous Neurologic (high
infusion dose) Metabolizes in tissues by or 1–3 Conjunctivitis deamination g/m2 dose IV (high dose) bolus Noncardiogenic pulmonary edema Azacytidine 750 Marrow Use limited to mg/m2 per leukemia Nausea week Altered Liver or methylation of DNA 150–200 Neurologic alters gene mg/m2 per expression Myalgia day x5–10 (bolus) or (continuous IV) Gemcitabine 1000 Marrow mg/m2 IV Nausea
weekly x7 Hepatic Fever/"flu syndrome" Fludarabine 25 Marrow Dose phosphate mg/m2 IV qd reduction with renal Neurologic x5 failure Lung Metabolized to F-ara converted to F-ara ATP in cells by deoxycytidine kinase Asparaginase 25,000 Protein synthesis Blocks IU/m2 q3–4 methotrexate action Clotting factors weeks Glucose or 6000 IU/m2 Albumin per day qod Hypersensitivity
for 3–4 weeks CNS or Pancreatitis 1000–2000 Hepatic 2 IU/m for 10– 20 days Pemetrexed 200 Anemia Supplement mg/m2 q3 folate/B12 Neutropenia weeks Caution in Thrombocytopen renal failure ia Antimitotic agents Vincristine 1–1.4 Vesicant Hepatic mg/m2 per clearance Marrow week Dose Neurologic reduction for GI: bilirubin >1.5 mg/dL
ileus/constipation; Prophylactic bladder hypotoxicity; bowel regimen SIADH Cardiovascular Vinblastine 6–8 Vesicant Hepatic mg/m2 per clearance Marrow week Dose Neurologic (less reduction as with common but similar vincristine spectrum to other vincas) Hypertension Raynaud's Vinorelbine 15–30 Vesicant Hepatic mg/m2 per clearance Marrow week Allergic/broncho