340 A Guide to Combination Cancer Chemotherapy Regimens Acute Myelogenous (AML) Cytarabine and Daunorubicin (7 plus 3) Cytarabine and Daunorubicin (7 plus 3) Regimen1-3 Drug Dose Route Administered on day(s) Total dose/cycle 1 2 3 4 5 6 7 Daunorubicin 45 to 90 mg/m2 IV X X X 135 to 270 mg/m2 Cytarabine 100 to 200 mg/m2 CIVI X X X X X X X 700 to 1400 mg/m2 If necessary, repeat when hematologic recovery is complete. CONSTITUENT DRUGS TOXICITIES Cytarabine (Cytosar-U) • Common (> 50%) • Daunorubicin (Cerubidine) • Hematologic Anemia SYNONYMS Grade 3 or 4: 77%2 • 7 + 3 Leukopenia • 7 plus 3 Grade 3 or 4: 98%2 Neutropenia USES Grade 3 or 4: 95%2 • Induction therapy for acute myelogenous leukemia Grade 3 or 4 febrile neutropenia: 35% to (AML), excluding acute promyelocytic leukemia1-3 36%2 Thrombocytopenia SUPPORTIVE CARE Grade 3 or 4: 98%2 Emetogenicity • Infection • Predicted: 30% to 90% (moderate) (see p. 519) Grade 3 or 4: 83%3 Hydration Neutropenic infection 2 • No special precautions required. Grade 3 or 4: 49% Hypersensitivity Precaution Infrequent (5% to 19%) • Daunorubicin (see p. 521) • Cardiovascular Cardiac event Myeloid Growth Factors Grade 3 or 4: 8%2 • Febrile neutropenia is an expected complication in Decrease in left ventricular ejection fraction: AML, especially following induction chemotherapy. 1%2 • Grade 3 or 4 febrile neutropenia rates of 35% to Hemorrhage 2 36% were reported in the studies reviewed. Grade 3 or 4: 10%2 In AML, use of myeloid growth factors is usually • • Dermatologic limited to postinduction supportive care in selected Rash or desquamation older patients.1 Grade 3 or 4: 5%2 Extravasation • Gastrointestinal • Daunorubicin (see p. 522) Anorexia Leukemias 341 Grade 3 or 4: 9%2 abnormal values of leukocytes, granulocytes, Nausea neutrophils, hemoglobin/hematocrit, and platelets, Grade 3 or 4: 6%2 pretreatment values for these hematologic • Metabolic parameters are used to monitor the disease, not to Fatigue determine fitness for chemotherapy. Grade 3 or 4: 6%2 Fever DOSAGE MODIFICATIONS Grade 3 or 4: 7%2 Renal Function (see p. 526) • Pulmonary Dyspnea Liver Function (see p. 531) 2 Grade 3 or 4: 5% Myelosuppression 2 • Treatment-related mortality, all causes: 5% Because the goal of AML induction chemotherapy 2 • Infection: 2% is bone marrow aplasia, no dose adjustments 2 Pulmonary failure: 0.9% are made for leukocyte, granulocyte, neutrophil, 2 Cardiac failure: 0.6% hemoglobin/hematocrit, or platelet values 2 Hemorrhage: 0.5% determined prior to therapy. Hypotension: 0.3%2 2 Ileus: 0.2% REFERENCES 3 • 30-day mortality, all causes: 12% 1. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology. Acute myeloid leukemia. RECOMMENDED LABORATORY TESTS v.2.2011. NCCN Web site. http://www.nccn.org. Ac- Baseline cessed December 2, 2010. • AST/ALT 2. Fernandez HF, Sun Z, Yao X, et al. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med. • Total bilirubin 2009;361(13):1249-1259. • Serum creatinine 3. Löwenberg B, Ossenkoppele GJ, van Putten W, et al; • CBC with differential Dutch-Belgian Cooperative Trial Group for Hemato- Prior to Each Induction Cycle Oncology (HOVON); German AML Study Group (AMLSG); • AST/ALT Swiss Group for Clinical Cancer Research (SAKK) • Total bilirubin Collaborative Group. High-dose daunorubicin in older • Serum creatinine patients with cute myeloid leukemia. N Engl J Med. • CBC with differential 2009;361(13):1235-1248. Recommended Pretreatment Values • Because AML often presents with extremely .