RANDOMIZED COMPARISON OF DAT VERSUS ADE AS INDUCTION CHEMOTHERAPY IN CHILDREN AND YOUNGER ADULTS WITH ACUTE MYELOID-LEUKEMIA - RESULTS OF THE MEDICAL-RESEARCH COUNCILS 10TH AML TRIAL (MRC AML10)

The relative efficacy and toxicity of the chemotherapeutic agents thio guanine (6TG) and etoposide (VP16) were assessed by a randomized compa rison of the DAT (daunorubicin, cytarabine, thioguanine) versus ADE (d aunorubicin, cytarabine, etoposide) regimens in the Medical Research C ouncil's 10th acute myeloid leukaemia trial (MRC AML 10), which was op en to patient entry from May 1988 to April 1995. In this, the largest reported trial of AML therapy to date, 1,857 eligible patients, mostly less than 56 years old, were randomized: 929 (including 143 children under 15 years old) were allocated to DAT and 928 (143 children) to AD E. The two groups were well matched for presentation features. The com plete remission (CR) rate was 81% with DAT and 83% with ADE (P =.3). T he percentages of remitters achieving remission after 1, 2, or more th an 2 courses were 70%, 22%, and 8% for DAT and 74%, 21%, and 5% for AD E. The percentages failing to achieve a CR due to resistant disease we re 11% with DAT versus 9% with ADE (P =.07). There was a slightly high er death rate in CR during consolidation chemotherapy with ADE (9%) th an with DAT (6%) (P =.06). Patients receiving DAT took slightly but si gnificantly longer to recover from neutropenia and thrombocytopenia bu t the median number of days in hospital were similar in each group. AD E patients experienced slightly more severe nonhematologic toxicity. T here was also no significant difference between the groups in the long er-term measures of efficacy: disease-free survival at 6 years from CR was 42% (+/-4) for DAT and 43% (+/-4) for ADE (P =.8); relapse rate a t 6 years was 50% (+/-4) for DAT and 49% (+/-5) for ADE (P = .6); surv ival at 6 years was 40% (+/-4) for both DAT and ADE (P =.9). Subgroup analysis failed to show any benefit for etoposide in patients with mon ocytic or myelomonocytic disease, or in any other diagnostic subgroup. In conclusion, DAT and ADE both achieve high remission rates and good long-term survival, and are equally effective chemotherapy regimens f or the treatment of AML patients aged up to 55 years. (C) 1997 by The American Society of Hematology.