Addition of Androgens Improves Survival in Elderly Patients With Acute Myeloid Leukemia: A GOELAMS Study

2017
Purpose Elderly patients with acute myeloid leukemia (AML) have a poor prognosis, and innovative maintenance therapycould improve their outcomes. Androgens, used in the treatment of aplastic anemia, have been reported to block proliferation of and initiate differentiation in AML cells. We report the results of a multicenter, phase III, randomized open-label trial exploring the benefit of adding androgens to maintenance therapyin patients 60 years of age or older. Patients and Methods A total of 330 patients with AML de novo or secondary to chemotherapy or radiotherapy were enrolled in the study. Induction therapy included idarubicin8 mg/m 2 on days 1 to 5, cytarabine100 mg/m 2 on days 1 to 7, and lomustine200 mg/m 2 on day 1. Patients in complete remission or partial remission received six reinduction courses, alternating idarubicin8 mg/m 2 on day 1, cytarabine100 mg/m 2 on days 1 to 5, and a regimen of methotrexate and mercaptopurine. Patients were randomly assigned to receive norethandrolone10 or 20 mg/day, according to body weight, or no norethandrolonefor a 2-year maintenance therapyregimen. The primary end point was disease-free survival by intention to treat. Secondary end points were event-free survival, overall survival, and safety. This trial was registered at www.ClinicalTrials.gov identifier NCT00700544. Results Random assignmentallotted 165 patients to each arm; arm A received norethandrolone, and arm B did not receive norethandrolone. Complete remission or partial remission was achieved in 247 patients (76%). The Schoenfeld time-dependent model showed that norethandrolonesignificantly improved survival for patients still in remission at 1 year after induction. In arms A and B, respectively, 5-year disease-free survival was 31.2% and 16.2%, event-free survival was 21.5% and 12.9%, and overall survival was 26.3% and 17.2%. Norethandroloneimproved outcomes irrelevant to all prognosis factors. Only patients with baseline leukocytes. 30 3 10 9 /L did not benefit from norethandrolone. Conclusion This study demonstrates that maintenance therapywith norethandrolonesignificantly improves survival in elderly patients with AML without increasing toxicity.
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