MITOXANTRONE VERSUS DAUNORUBICIN IN INDUCTION-CONSOLIDATION CHEMOTHERAPY - THE VALUE OF LOW-DOSE CYTARABINE FOR MAINTENANCE OF REMISSION, AND AN ASSESSMENT OF PROGNOSTIC FACTORS IN ACUTE MYELOID-LEUKEMIA IN THE ELDERLY - FINAL REPORT OF THE LEUKEMIA COOPERATIVE GROUP OF THE ANIZATION-FOR-THE-RESEARCH-AND-TREATMENT-OF-CANCER AND THE DUTCH-BELGIAN HEMATOONCOLOGY COOPERATIVE HOVON GROUP RANDOMIZED PHASE-III STUDY AML-9

Purpose and Methods: Optimization of remission-induction and postremis sion therapy in elderly individuals with acute myeloid leukemia (AML) was the subject of a randomized study in patients older than 60 years. Remission-induction chemotherapy was compared between daunomycin (DNR ) 30 mg/m(2) on days 1, 2, and 3 versus mitoxantrone (MTZ) 8 mg/m(2) o n days 1, 2, and 3, both plus cytarabine (Ara-C) 100 mg/m(2) on days 1 to 7. Following complete remission (CR), patients received one additi onal cycle of DNR or MTZ chemotherapy and were then eligible for a sec ond randomization between eight cycles of low-dose (LD)-Ara-C 10 mg/m( 2) subcutaneously every 12 hours for 12 days every 6 weeks or no furth er treatment. Results: A total of 242 patients was randomized to DNR a nd 247 to MTZ. Median age of both study groups was 68 years. Secondary AML was documented in 26% and 25% of patients in either arm. The prob ability of attaining CR was greater (P = .069) with MTZ (47%) than wit h DNR (38%). Median duration of neutropenia was 19 (DNR) and 22 days ( MTZ). The greater response rate to MTZ therapy correlated with reduced occurrence of chemotherapy resistance (32% v 47%, P = .001). With a m edian follow up of 6 years, 5-year disease-free survival (DFS) is 8% i n each arm. Overall survival estimates are not different between the g roups (6% v 9% at 5 yrs). Poor performance status at diagnosis, high W BC count, older age, secondary AML, and presence af cytogenetic abnorm alities all had an adverse impact on survival. Secondary AML and abnor mal cytogenetics predicted for shorter duration of CR. Among complete responders, 74 assessable patients were assigned to Ara-C and 73 ta no further therapy Actuarial DFS was significantly longer (P = .006) for Ara-C- treated (13% [SE = 4.0%] at 5 years) versus nontreated patient s (7% [58=3%]), but overall survival was similar (P = .29): 18% (SE = 4.6%) versus 15% (SE = 4.3%). Metaanalysis on the value of Ara-C postr emission therapy confirms these results. Conclusion: In previously unt reated elderly patients v induction therapy produces a slightly better CR rate than does a DNR-containing regimen, but it has no significant effect on remission duration and survival. Ara-C in maintenance may p rolong DFS, but it did not improve survival. (C) 1998 by American Soci ety of Clinical Oncology.