The addition of norethandrolone as maintenance therapy improved survival in patients aged ≥ 60 years with acute myeloid leukemia (AML), according to a French phase III trial reported in the Journal of Clinical Oncology by Pigneux et al.
Norbert Ifrah, MD, of CHU d’Angers, France, is the corresponding author of the Journal of Clinical Oncology article.
In the open-label trial, 330 patients with de novo AML or disease secondary to chemotherapy or radiotherapy were randomized between June 2002 and January 2005 to receive maintenance norethandrolone (n = 165) or no norethandrolone (n = 165) for 2 years. Patients first received induction therapy with idarubicin, cytarabine, and lomustine. Patients in complete or partial remission received six reinduction courses alternating idarubicin, cytarabine, and a regimen of methotrexate and mercaptopurine. Maintenance norethandrolone was given at 10 or 20 mg/d, according to body weight.
Outcomes and Toxicity
A time-dependent model showed that norethandrolone treatment was associated with significantly improved survival among patients still in remission at 1 year after induction. Among 230 patients who achieved complete remission (71%, 111 in the norethandrolone group and 119 in the no norethandrolone group), 5-year disease-free survival was 31.2% in the norethandrolone group vs 16.2% in the no norethandrolone group (P = .002). From the time of study inclusion, 5-year event-free survival was 21.5% vs 12.9% (P = nonsignificant), and 5-year overall survival was 26.3% vs 17.2% (P = .008). Norethandrolone was associated with improved outcomes irrespective of most prognostic factors; there was no benefit of norethandrolone among patients with baseline leukocytes > 30 x 109/L.
With regard to postremssion toxicity, no differences between the norethandrolone and no norethandrolone groups were observed for rehospitalization, need for transfusion, or grade 3 or 4 adverse events. Secondary cancers were observed in 11 vs 15 patients, with no prostate cancers observed.
The investigators concluded: “This study demonstrates that maintenance therapy with norethandrolone significantly improves survival in elderly patients with AML without increasing toxicity.”