Non-infusional vs intravenous consolidation chemotherapy in elderly patients with acute myeloid leukemia: final results of the EORTC-GIMEMA AML-13 randomized phase III trial

In this trial, acute myeloid leukemia patients ( pts) aged 61-80 years received MICE ( mitoxantrone, etoposide and cytarabine) induction chemotherapy in combination with different schedules of granulocyte colony-stimulating factor administration. Pts in complete remission were subsequently randomized for two cycles of consolidation therapy: mini-ICE regimen ( idarubicin, etoposide and cytarabine) given according to either an intravenous ( i.v.) or a 'non-infusional' schedule. Among the 346 pts randomized for the second step, 331 pts received consolidation-1 and 182 consolidation-2. A total of 290 events ( 255 relapses, 35 deaths in first CR) have been reported. The median follow-up was 4.4 years. No significant differences were detected in terms of disease-free survival ( median 9 vs 10.4 months, P = 0.15, hazard ratio ( HR) = 1.18, 95% confidence interval ( CI) 0.94-1.49) - primary end point - and survival ( median 15.7 vs 17.8 months, P = 0.19, HR = 1.17, 95% CI 0.92-1.50). In the 'non-infusional' arm grade 3-4 vomiting ( 10 vs 2%; P = 0.001) and diarrhea ( 10 vs 4%; P = 0.03) were higher than in the 'i.v.' arm, whereas time to platelet recovery > 20 x 10(9)/I ( median: 19 vs 23 days; P = 0.02) and duration of hospitalization ( mean: 15 vs 27 days; P < 0.0001) was shorter. The 'noninfusional' consolidation regimen resulted in an antileukemic effect similar to the intravenous regimen, which was less myelosuppressive and associated with less hospitalization days.