Chapter 081. Principles of Cancer Treatment (Part 11) Table 81-2 Commonly Used Cancer Chemotherapy Agents Drug Exam ples of Usual Doses Toxicity Interactions, Issues Direct DNA-Interacting Agents Alkylators Cyclophospha 400– 2000 mg/m 2 Marrow (relative Liver metabolism required mide IV 100 mg/m 2 PO qd platelet sparing) Cystitis Common alkylator a Cardiac (high dose) to activate to phosphoramide mustard + acrolein Mesna protects against "high- dose" bladder damage Mechloretha mine 6 mg/m 2 IV day 1 and day 8 Marrow Vesicant Nausea Topical use in cutaneous lymphoma Chlorambucil 1–3 mg/m 2 qd PO Marrow Common alkylator a Melphalan 8 mg/m 2 qd x 5, PO Marrow (delayed nadir) Decreased renal function delays clearance GI (high dose) Carmustine (BCNU) 200 mg/m 2 IV 150 mg/m 2 PO Marrow (delayed nadir) GI, liver (high dose) Renal Lomustine (CCNU) 100– 300 mg/m 2 PO Marrow (delayed nadir) Ifosfamide 1.2 g/m 2 per day qd x 5 + mesna Myelosuppressiv e Bladder Neurologic Metabolic acidosis Isomeric analogue of cyclophosphamide More lipid soluble Greater activity vs testicular Neuropathy neoplasms and sarcomas Must use mesna Procarbazine 100 mg/m 2 per day qd x14 Marrow Nausea Neurologic Common alkylator a Liver and tissue metabolism required Disulfiran- like effect with ethanol Acts as MAOI HBP after tyrosinase-rich foods Dacarbazine (DTIC) 375 mg/m 2 IV day 1 and day 15 Marrow Nausea Metabolic activation Flulike Temozolomid e 150– 200 mg/m 2 qd x 5 q28d or 75 mg/m 2 qd x 6–7 weeks Nausea/vomiting Headache/fatigue Constipation Infrequent myelosuppression Altretamine (formerly hexamethylmelamin e) 260 mg/m 2 per day qd x14– 21 as 4 divided oral doses Nausea Neurologic (mood swing) Neuropathy Marrow (less) Liver activation Barbiturates enhance/cimetidine diminishes Cisplatin 20 mg/m 2 qd x5 IV 1 q3– 4 weeks or 100–200 mg/m 2 per Nausea Neuropathy Auditory Marrow platelets Maintain high urine flow; osmotic diuresis, monitor intake/output K + , Mg 2+ dose IV q3– 4 weeks > WBCs Renal Mg 2+ , Ca 2+ Emetogenic— prophylaxis needed Full dose if Cr Cl > 60 mL/min and tolerate fluid push Carboplatin 365 mg/m 2 IV q3– 4 weeks as adjusted for CrCl Marrow platelets > WBCs Nausea Renal (high dose) Reduce dose according to CrCl: to AUC of 5– 7 mg/mL per min [AUC = dose/(CrCl + 25)] Oxaliplatin 130 mg/m 2 q3 weeks over 2 h or 85 mg/m 2 q2 weeks Nausea Anemia Acute reversible neurotoxicity; chronic sensory neurotox cumulative with dose; reversible laryngopharyngeal spasm Antitumor antibiotics Bleomycin 15–25 mg/d qd x5 IV bolus or continuous IV Pulmonary Skin effects Raynaud's Hypersensitivity Inactivate by bleomycin hydrolase (decreased in lung/skin) O 2 enhances pulmonary toxicity Cisplatin- induced decrease in CrCl may increase skin/lung toxicity Reduce dose if CrCl < 60 mL/min Actinomycin 10–15 µg/kg per day Marrow Radiation D qd x5 IV bolus Nausea Mucositis Vesicant Alopecia recall Mitomycin C 6–10 mg/m 2 q6 weeks Marrow Vesicant Hemolytic- uremic syndrome Lung CV—heart failure Treat superficial bladder cancers by intravesical infusion Delayed marrow toxicity Cumulative marrow toxicity Etoposide (VP16-213) 100– 150 mg/m 2 IV qd x3–5d or 50 Marrow (WBCs > platelet) Alopecia Hepatic metabolism—renal 30% Reduce doses mg/m 2 PO qd x21d or up to 1500 mg/m 2 per dose (high dose with stem cell support) Hypotension Hypersensitivity (rapid IV) Nausea Mucosit is (high dose) with renal failure Schedule- dependant (5 day better than 1 day) Late leukemogenic Accentuate antimetabolite action Topotecan 20 mg/m 2 IV q3– 4 weeks over 30 min or 1.5– 3 mg/m 2 q3– 4 weeks over 24 h or 0.5 mg/m 2 per Marrow Mucositis Nausea Mild alopecia Reduce dose with renal failure No liver toxicity day over 21 days Irinotecan (CPT II) 100– 150 mg/m 2 IV over 90 min q3– 4 weeks or 30 mg/m 2 per day over 120 h Diarrhea: "early onset" with cramping, flushi ng, vomiting; "late onset" after several doses Marrow Alopecia Nausea Vomiting Pulmonary Prodrug requires enzymatic clearance to active drug "SN 38" Early diarrhea likely due to biliary excretion Late diarrhea, use "high- dose" loperamide (2 mg q2–4 h) Doxorubicin and daunorubicin 45–60 mg/m 2 dose q3–4 weeks or 10– Marrow Mucositis Alopecia Heparin aggregate; coadministration increases clearance [...]... deficiency increases toxicity Metabolizes in tissues Capecitabine 665 mg/m2 Diarrhea bid Prodrug 5FU due of to Hand-foot continuous; intratumoral syndrome 1250 2 mg/m metabolism bid 2 weeks on/ 1 off; 829 mg/m2 bid 2 weeks on/ 1 off + 60 mg/d leucovorin Cytosine arabinoside 100 mg/m2 Marrow per Enhances activity of alkylating Mucositis day qd x7 by continuous agents Neurologic (high infusion dose) Metabolizes... (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 mg/m2 ycin IV Excretes in urine Immunosuppressi every other on Reduce dose week for renal failure Neurologic Inhibits Renal adenosine deaminase 6- 75 Marrow Variable Mercaptopurine mg/m2... 1–3 tissues by Conjunctivitis g/m2 dose IV (high dose) deamination bolus Noncardiogenic pulmonary edema Azacytidine 750 mg/m2 Marrow per Use limited to leukemia Nausea week Altered Liver or methylation of DNA Neurologic 150–200 mg/m2 per expression Myalgia day x5–10 (bolus) or (continuous IV) Gemcitabine 1000 mg/m2 alters Marrow IV Nausea gene weekly x7 Hepatic Fever/"flu syndrome" Fludarabine phosphate... Rash Neutropenia Thrombocytopen ia Sorafenib 400 Diarrhea mg PO bid Hand-foot syndrome Other rash Sunitinib 50 mg PO qd for 4 1 h before, 2 h after meals Diarrhea Dasatinib documented benefit Fatigue of 6 weeks Diarrhea Neutropenia Miscellaneous Arsenic trioxide 0.16 mg/kg Up QTc per APL differentiation Peripheral day up to 50 syndrome (see under neuropathy days in APL tretinoin) Musculoskeletal pain... factor; GI, gastrointestinal; HBP, high blood pressure; MAOI, monoamine oxidase inhibitors; MI, myocardial infarction; 6MP, 6-mercaptopurine; NSAIDs, nonsteroidal anti-inflammatory drugs; SIADH, syndrome of inappropriate antidiuretic hormone; WBCs, white blood cells . Chapter 081. Principles of Cancer Treatment (Part 11) Table 81-2 Commonly Used Cancer Chemotherapy Agents Drug Exam ples of Usual Doses Toxicity Interactions,. continuous; 1250 mg/m 2 bid 2 weeks on/ 1 off; 829 mg/m 2 bid 2 weeks on/ 1 off + 60 mg/d leucovorin Diarrhea Hand-foot syndrome Prodrug of 5FU due to intratumoral metabolism Cytosine. Marrow platelets > WBCs Nausea Renal (high dose) Reduce dose according to CrCl: to AUC of 5– 7 mg/mL per min [AUC = dose/(CrCl + 25)] Oxaliplatin 130 mg/m 2 q3 weeks over 2 h or