Chemomodulation of sequential high-dose cytarabine by fludarabine in relapsed or refractory acute myeloid leukemia: a randomized trial of the AMLCG

Chemomodulation of cytarabine by fludarabine has been attributed with a higher antileukemic efficacy, but randomized trials to address this question are rare. We therefore conducted a multicenter, randomized phase III study to evaluate the antileukemic efficacy of adding fludarabine to sequential high-dose cytarabine+idarubicin (SHAI) re-induction chemotherapy in relapsed or refractory acute myeloid leukemia (AML). Patients ( n =326, of which 281 were evaluable) were randomly assigned to SHAI (cytarabine, 1 g/m 2 bid, days 1–2 and 8–9 (3 g/m 2 for patients ⩽60 years with refractory AML or ⩾2nd relapse); idarubicin 10 mg/m 2 daily, days 3–4 and 10–11) or F-SHAI (SHAI with fludarabine, 15 mg/m 2 , 4 h before cytarabine). Although complete remission (CR) rates (35% SHAI and 44% F-SHAI) and overall survival did not differ between both regimens, fludarabine prolonged time to treatment failure from 2.04 to 3.38 months (median, P