A RANDOMIZED STUDY OF HIGH-DOSE CYTARABINE IN INDUCTION IN ACUTE MYELOID-LEUKEMIA

High-dose cytarabine (ara-c) may overcome cytarabine resistance in leu kemic blasts. It has been used as a successful salvage and in postremi ssion therapy but not as initial induction treatment. Patients aged 15 to 60 years, presenting with newly diagnosed acute myeloid leukemia ( AML) were randomized to receive either high-dose cytarabine, 3 g/m(2) 12 hourly on days 1, 3, 5, and 7 for 8 doses, daunorubicin 50 mg/m(2) days 1 to 3, etoposide 75 mg/m(2) days 1 to 7, (HIDAC-3-7) or standard dose cytarabine 100 mg/m(2) continuous intravenous infusion for 7 day s with daunorubicin and etoposide at the same dose and schedule as abo ve (7-3-7). Patients could receive a second or third induction course if complete remission (CR) was not achieved. All patients received the same postinduction consolidation therapy (5-2-5) for 2 courses. Eligi ble patients had no prior chemotherapy or myelodysplastic disease. Pat ients have been followed for a median of 4.5 years. Of 301 patients tr eated, complete response (CR) was achieved in 71% with HIDAC-3-7 and 7 4% with 7-3-7. For patients in CR, the estimated median remission dura tion was 45 months with HIDAC-3-7 and 12 months with 7-3-7 (P = .0005 univariate analysis, P = .0004 multivariate analysis). The estimated p ercentage of patients relapse free 5 years after achieving a CR was 49 % on HIDAC-3-7 and 24% on 7-3-7. Patients in CR tended to survive long er with HIDAC-3-7 but there were no overall survival differences betwe en the two arms. HIDAC-3-7 was associated with significantly more toxi city in induction with more leukopenia, thrombocytopenia, nausea, and vomiting and eye toxicity (all P < .001) but a similar incidence of se vere central nervous system and cerebellar toxicity compared to 7-3-7. The consolidation treatment was the same in both arms but caused sign ificantly more leukopenia and thrombocytopenia in patients previously treated with HIDAC-3-7 induction (P < .0001). We conclude that a dose- effect exists for cytarabine in AML and that HIDAC-3-7 prolongs remiss ion duration and disease-free survival and is tolerable when used as i nitial induction therapy in patients with de novo AML. (C) 1996 by The American Society of Hematology.