A Multicenter Randomized Comparison of Maintenance Treatment with Androgens in Elderly Acute Myeloid Leukemia after ICL Regimen as Induction Therapy: Results of the Goelams-2002 Study.

In an attempt to improve the outcome of acute myeloid leukemia in older patients, we performed a multicenter randomized trial evaluating the possible benefit of androgens during post remission therapy. All patients received the ICL regimen as induction (Idarubicin, 8mg/m² d1–5; Cytarabine, 100mg/m² d1–7 and Lomustine, 200mg/m² d1). All patients were randomized at the time of diagnosis to receive, after achieving CR or PR, a maintenance therapy including or not androgens. Maintenance therapy consisted of 6 courses of reinduction with idarubicin (8mg/m² d1) and cytarabine (100mg/m²d1–5, subcutaneously) every 3 months, and, between these courses, a continuous regimen of methotrexate and 6-mercaptopurine. Patients randomized with androgens additionally received 10 to 20 mg according to body weigh of norethandrolone daily from CR/PR on, for up to 2 years. Between June 2002 and January 2005, 330 patients aged ≥ 60 years (median 70 yrs, range 60–86) were included. CR, PR, failure and death rates after induction were 69 %, 6%, 9% and 15% respectively. The median follow-up for the 330 patients was 26 months.

Among the 249 patients who achieved remission, 119 had been randomized with norethandrolone and 130 without. The 2 arms were balanced according to age, sex-ratio, performance status, FAB, WBC as well as platelets counts, peripheral blood and bone marrow blasts counts and cytogenetic groups (low risk: t(8;21), inv(16); high risk: del(5), del(7), del(11q), complex karyotype; standard-risk: normal karyotype and other aberrations). Differences in CR rates were only related to the latter parameter of cytogenetic features (P = 0.005).

For the whole cohort of patients DFS at 3-years was 23±3% (median 13 months) and OS at 3 years was 29±3% (median 15 months). For patients who achieved CR or PR and had been randomized, the addition of androgens did not influence either DFS (P = 0.6) or OS (P = 0. 9), even when considering age groups, high/low WBC, or cytogenetic features.

In conclusion, the ICL regimen followed by six reinductions and two years maintenance therapy induce high CR rates and improve OS and DFS. However the addition of androgens did not decrease the relapse rate.