Sequential response-adapted induction and consolidation regimens idarubicin/cytarabine and mitoxantrone/etoposide in adult acute myelogenous leukemia: 10 year follow-up of a study by the Canadian Leukemia Studies Group

Purpose. The Canadian Leukemia Studies Group (CLSG) sought to test the safety and efficacy of response-adapted, non-cross resistant chemotherapy in de novo acute myeloid leukemia (AML). The combinations of idarubicin 12 mg/m²/d on days 1 - 3 and Ara-C (200 mg/ m²/d) on days 1 - 7 (IDAC) followed by mitoxantrone 10 mg/ m²/day, and etoposide 100 mg/m²/day, on days 1 - 5 (NOVE) were used according to patient response to induction and consolidation. Patients and methods. In this multi-centre open-label phase II study, 140 patients up to age 80 were given induction with IDAC. Patients were entered between March 1993 and August 1995. If patients had persistent blasts at day 14 or on recovery, they were given NOVE. As consolidation, patients achieving complete remission (CR) with IDAC were given 1 further cycle of IDAC and 1 cycle of NOVE. Patients achieving CR after NOVE were given 2 further cycles of NOVE. Results. 76% of all patients achieved remission after IDAC +/- NOVE, 81% in patients aged ≤60 years and 67% in patients aged >60. Overall, induction mortality was 11% and toxicity was similar to other cooperative group studies. Median follow-up was 104.0 months with 95% CI: (100.0, 105.2). Median overall survival (OS) in responding patients ≤60 was not reached: Of the 79 responders ≤60, 35 died. The median disease free survival (DFS) in these responding patients was 22.7 (14.9, na) months. Median OS and DFS in responding patients >60 was 10.0 (7.3, 15.2) months and 7.5 (6.2, 15.2) months, respectively. Conclusion. The results of this trial are very encouraging and suggest that there may be long-term benefit to this method. On the basis of these results, a randomized phase III trial has been performed.