REMISSION INDUCTION THERAPY OF UNTREATED ACUTE MYELOID-LEUKEMIA USINGA NON-CYTARABINE-CONTAINING REGIMEN OF IDARUBICIN, ETOPOSIDE, AND CARBOPLATIN

BACKGROUND. The safety and efficacy of idarubicin, etoposide, and carb oplatin as remission induction therapy for patients younger than 60 ye ars with untreated acute myeloid leukemia was studied as an alternativ e to standard regimens based on cytarabine plus anthracycline. METHODS . Eligible patients received idarubicin (36-40 mg/m(2)), etoposide (50 0 mg/m(2)), and carboplatin (1000-1500 mg/m(2)) over 5 days. Those who achieved complete remission received a single course of cytarabine 1. 5 gm/m(2) every 12 hours for a total of 12 doses. D-xylose absorption was studied as a marker for cytotoxic therapy-induced gut mucosal dama ge. Cytogenetic and immunophenotyping studies were performed at the ti me of diagnosis and examined for prognostic importance. RESULTS. Remis sion was achieved in 29 (67%) of 43 patients with a single induction c ourse. The median leukemia free and overall survival times were 15.4 m onths (95% CI 6.5-24.2) and 12.5 months (95% CI 5.9-19.1), respectivel y. Induction mortality was 14%. Karyotype (normal, simple, or complex vs. very complex) was the strongest predictor of remission (79% vs. 25 %, P = 0.01), leukemia free survival (odds ratio [OR] 19.3, 95% CI 2.7 -138.9), and overall survival (OR 5.4, 95% CI 2.1-13.9). Dose-limiting gut mucosal toxicity was greatest during Weeks 2 and 3. Bloodstream i nfections occurred in 49% of patients at a median of 12 days. Grade 3- 4 diarrhea, nausea, stomatitis, esophagitis/dysphagia, and vomiting de veloped in 33%, 26%, 23%, 9%, and 2% of cases, respectively, at a medi an of 17, 16, 11, 15.5, and 21 days, respectively. CONCLUSIONS. This r egimen was active in adults younger than 60 years with untreated acute myeloid leukemia and normal, simple, or complex karyotypes. Remission duration was confounded by karyotype. Mucosal toxicity limited the to lerability of this regimen. These adverse effects might be overcome by increasing the intensity of postremission therapy and modifying the d osing schedule. Cancer 1998;83:1344-54. (C) 1998 American Cancer Socie ty.