Maintenance therapy with norethandrolone may improve survival in elderly patients with acute myeloid leukemia (AML) without increasing toxicity, according to a study published in the Journal of Clinical Oncology. 

Patients over the age of 60 years diagnosed with AML have a poor prognosis, with only 15% surviving 5 years. Clinicians must also take care to balance the benefits of potential treatments with toxicity, as many in this demographic may present with other comorbidities, which can make it difficult for them to tolerate some regimens. Prior studies have shown that androgens used for the treatment of aplastic anemia may also have value for elderly patients with AML.

In a study led by Arnaud Pigneux, MD, Centre Hospitalier Universitaire Bordeaux, France, researchers conducted a multicenter, phase III study to assess the efficacy of androgens for patients with AML versus no androgens.

A total of 330 patients were enrolled in the study. After being treated with standard therapy, patients were randomly assigned to received norethandrolone 10 mg per day, norethandrolone 20 mg per day, or no norethandrolone for a 2-year maintenance period. The primary endpoint was disease-free survival (DFS), although event-free survival (EFS) and overall survival (OS) were also measured.

Overall, 76% of patients achieved a response, with 70% achieving complete remission. Treatment failure occurred in only 8% of patients. Additionally, DFS in those treated with norethandrolone was almost twice as high as what was observed in those who did not receive the drug (31.2% vs 16.2%). EFS (21.5% vs 12.9%) and OS (26.3% vs 17.2%) rates were also increased among patients assigned norethandrolone. There were no differences between the treatment arms for rehospitalizations, need for transfusions, or grade 3 or 4 toxicities, incidence of secondary cancer was also similar in both groups.

Using an extended Cox model to consider time-dependent covariables to compare treatments arms in patient subgroups, researchers found some interesting trends related to patient circumstances and use of norethandrolone.

“In choosing to add androgens to post-remission therapy, we expected to improve DFS, which was achieved, yet a beneficial effect was finally observed for EFS and OS,” said Dr Pigneux. “This beneficial effect was intriguingly time dependent and became significant only among patients who had failed to relapse during the first year of therapy.”

Also, they found that the identification of diagnostic hyperleukocytosis may be a prognostic factor in this setting, as benefit derived from the addition of norethandrolone as maintenance therapy was observed in all patients except those with a white blood cell count greater than 30 × 109/L at diagnosis.

Researchers concluded that maintenance therapy with norethandrolone significantly improved survival in elderly patients with AML without increasing toxicity.