Comparison of idarubicin plus ara-C-, fludarabine plus ara-C-, and topotecan plus ara-C-based regimens in treatment of newly diagnosed acute myeloid leukemia, refractory anemia with excess blasts in transformation, or refractory anemia with excess blasts

It has been unclear whether regimens containing topotecan + ara-C (TA) or f ludarabine + ara-C (FA) idarubicin are superior to regimens containing idar ubicin + ara-C (IA) without either fludarabine or topotecan for treatment o f newly diagnosed acute myeloid leukemia (AML), refractory anemia with exce ss blasts in transformation (RAEB-t), or RAEB. Of 1279 patients treated her e for these diagnoses between 1991 and 1999, 322 received IA regimens, 600 FA regimens, and 357 TA regimens. All regimens used ara-C doses of 1 to 2 g m/m(2)/d, given by continuous infusion in IA, and over 2 to 4 hours in FA a nd TA. Complete remission (CR) rates were lower with FA (55%) and TA (59%) than with IA (77%). Both event-free survival (EFS) in CR and survival were shorter: median EFS in CR (95% confidence interval) was 63 weeks (range, 55 -76 weeks) for IA, 40 (range, 31-46 weeks) for FA, and 36 (range, 27-44 wee ks) for TA; median survival was 77 weeks (range, 57-88 weeks) for IA, 30 (r ange, 27-35 weeks) for FA, and 41 (range, 35-50 weeks) for TA. These trials were not randomized, disproportionately given the FA and TA regimens. None theless, after accounting for prognosis the FA and TA regimens remained hig hly significantly associated with lower CR rates, shorter EFS in CR, and sh orter survival. Accounting for possible effects of individual trials within each of the IA, FA, and TA groups did not alter these findings. It is unli kely that, as given here, either FA or TA is, in general, superior to IA, h ighlighting the need for new treatments. (C) 2001 by The American Society o f Hematology.