Randomised unicenter trial for comparison of three regimens in de novo adult acute nonlymphoblastic leukaemia.

Various regimens have been explored in the treatment of acute nonlymphoblastic leukaemia (AML), but so far none has been shown to be superior. Here we report on a comparison of three widely used protocols defined by Berman (Group 1), MRC AML 10 (Group 2), and Arlin (Group 3). Group 1 includes cytosine arabinoside (Ara-C) (100 mg/m2/d, days 1-7) and idarubicin (Ida) (12 mg/m2/d, days 1-3) for induction, and Ara-C (200 mg/m2/d, days 1-6) and Ida (15 mg/m2/d, day 1) twice for consolidation. Group 2 includes Ara-C (200 mg/m2/d, days 1-10), daunorubicin (Dnc) (50 mg/m2/d, days 1, 3, 5) and etoposide (VP16) (100 mg/m2/d, days 1-5) for induction. The first consolidation therapy consisted of the same schedule except for Ara-C given on days 1-8. The second consolidation regimen consisted of Ara-C (200 mg/m2/d, days 1-8), VP16 (100 mg/m2/d, days 1-5) and amsacrine (100 mg/m2/d, days 1-5). Mitoxantrone (Mitox) (10 mg/m2/d, days 1-5) and Ara-C (200 mg/m2/d, days 1-3) were given as the third consolidation therapy. Group 3 was identical to Group 1 except for Ida being replaced with Mitox. During the study period 99 patients were enrolled and 34 were allocated randomly to Group 1, 36 to Group 2, and 29 to Group 3. Except for age distribution all patients' characteristics were similar between the groups. As there were more elderly patients in Group 1, time to complete remission (CR) was longer in this group as they needed more second induction. Induction deaths were 9.7%, 12.9% and 14.8% in Groups 1, 2 and 3, respectively. Patients in Group 2 received a higher amount of Ara-C compared with the other groups (P < 0.001). After a median follow-up period of 45 months (1-67 for survivors) an advantage in Group 1 was observed. Relapse-free survival (RFS) was better in Group 1 (P = 0.014) at 3 years. Fourteen of the patients were transplanted (11 allografts, 3 autografts). When patients with transplants were excluded, overall survival was longer in Group 1 both at 3 years and 5 years (P = 0.05). In conclusion, despite patient advanced age and lower dose of Ara-C, the idarubicin-containing treatment was superior to the other regimens.

RCT Entities:   Population Interventions Outcomes