Multicenter randomized phase II trial of idarubicin vs mitoxantrone, combined with VP-16 and cytarabine for induction consolidation therapy, followedby a feasibility study of autologous peripheral blood stem cell transplantation in elderly patients with acute myeloid leukemia

To compare the antileukemic efficacy of idarubicin and mitoxantrone in elde rly patients with acute myeloid leukemia (AML) and to evaluate the feasibil ity of autologous transplantation using PBSC after consolidation in those w ith a good performance status, 160 patients (median age 69 years), with AML at diagnosis, 118 of them with de novo AML and 42 with AML secondary to my elodysplastic syndrome or toxic exposure (sAML), received induction treatme nt with idarubicin, 8 mg/m(2)/day or mitoxantrone, 7 mg/m(2)/day, on days 1 ,3, and 5, both combined with VP-16, 100 mg/m(2)/day on days 1 to 3 and cyt arabine (araC), 100 mg/m(2)/day, on days 1 to 7. G-CSF, 5 mu g/kg/day, was administered after chemotherapy in patients aged more than 70 years. Patien ts in complete remission (CR) received one course of consolidation using th e same schedule as for induction except the araC administration was shorten ed to 5 days. Some patients younger than 70 years were then scheduled for a utologous stem cell harvest on days 5 to 7 of G-CSF, 5 mu g/kg/day, initiat ed after hematopoietic recovery from consolidation. Autologous transplantat ion was performed following an additional chemotherapy conditioning. Ninety -five patients (59%) achieved CR, without significant difference between th e idarubicin (56% CR) and mitoxantrone (63% CR) group. There was also no si gnificant difference in CR rate between de nova AML (63%) and secondary AML (55%) (P= 0.12). Patients aged <70 years had 67% CR, while patients aged g reater than or equal to 70 years had 49% (P= 0.02). There was no significan t difference in the duration of aplasia between the two arms. Median time t o neutrophil recovery was 22 days in patients who received G-CSF following induction and 27 days in patients who did not (P=0.006). Severe extra-hemat ologic toxicities of induction did not differ between the two arms and incl uded sepsis (39%), diarrhea (13%), hyperbilirubinemia (8%), hemorrhage (6%) and vomiting (6%). Overall, 14 patients (9%), died from toxicity of induct ion. First consolidation was administered in 74 patients of whom seven (9%) died from toxicity. Nineteen patients have received transplantation. Media n time to recovery of neutrophils >0.5 x 10(9)/1 was 13 days and of platele ts >50 x 10(9)/l 43 days following consolidation. There were two toxic deat hs. Median disease-free survival and survival from time of achieving CR of nan transplanted patients are 6 and 7 months respectively without differenc e between the two arms. Fourteen transplanted patients relapsed at a median of 5 months post-transplant. We conclude that this regimen is well tolerat ed and has a good efficacy to induce CR, without a significant difference i n efficacy and toxicity between idarubicin and mitoxantrone. Intensive post induction, including transplantation, is feasible; however, this procedure did not seem to prevent early relapse in the majority of patients. Neither the high rate of CR nor consolidation nor transplant procedure in a selecte d group of patients did translate into improved DFS and/or survival.