Maintenance therapy with norethandrolone significantly improved survival in elderly patients with acute myeloid leukemia without increasing toxicity.
Maintenance therapy with norethandrolone significantly improved survival in elderly patients with acute myeloid leukemia (AML) without increasing toxicity, according to the results of a GOELAMS study published in the Journal of Clinical Oncology. Patients assigned the treatment saw improvements in disease-free survival (DFS), event-free survival (EFS), and overall survival (OS).
“In choosing to add androgens to postremission therapy, we expected to improve DFS, which was achieved, yet a beneficial effect was finally observed for EFS and OS,” wrote Arnaud Pigneux, MD, of Centre Hospitalier Universitaire Bordeaux, France, and colleagues. “This beneficial effect was intriguingly time dependent and became significant only among patients who had failed to relapse during the first year of therapy.”
According to the study, patients aged older than 60 with AML have a poor prognosis and rarely achieve an OS of greater than 15% at 5 years. There is a need for treatments that can improve and prolong remission without increasing treatment-related mortality. Previous research had shown that androgens, used for the treatment of aplastic anemia, may be valuable for the treatment of AML without increasing toxicity.
Pigneux and colleagues conducted a multicenter, phase III study in 330 patients with AML. Patients had induction therapy with idarubicin 8 mg/m2 on days 1 to 5, cytarabine 100 mg/m2 on days 1 to 7, and lomustine 200 mg/m2 on day 1. Patients who achieved complete remission or partial remission received six reinduction courses alternating idarubicin 8 mg/m2 on day 1, cytarabine 100 mg/m2 on days 1 to 5, and a regimen of methotrexate and mercaptopurine. Patients were then randomly assigned to norethandrolone 10 or 20 mg per day or no norethandrolone for a 2-year maintenance period. The primary endpoint was DFS.
Overall response was achieved in 76% of patients; 267 patients (70.7%) achieved complete remission. Treatment failure occurred in 8% of patients.
“On the basis of previous results from our group, we had planned on 60% partial remission plus complete remission, whereas the observed rate was 76%,” the researchers wrote. “This was not linked to a different selection of patients or to different chemotherapy, but could be related to general recommendations for supportive care.”
The 5-year DFS was 31.2% for patients assigned norethandrolone compared with 16.2% for patients not given the maintenance therapy. EFS (21.5% vs 12.9%) and OS (26.3% vs 17.2%) were also increased among patients assigned norethandrolone.
The researchers used an extended Cox model considering time-dependent covariables to compare treatment arms in patient subgroups.
“This strategy allowed identification of diagnostic hyperleukocytosis as an additional prognostic factor in this setting,” the researchers wrote. “Indeed, benefit derived from the addition of norethandrolone as maintenance therapy was observed in all patients except those with a WBC count > 30 × 109/L at diagnosis.”
The researchers noted no differences between the treatment arms for rehospitalizations, need for transfusions, or grade 3 or 4 toxicities. Additionally, the incidence of secondary cancer was similar between both arms.