This article is more than 5 years old. Information may no longer be current.
Low-dose norethandrolone significantly improves survival for elderly patients with AML
Click Here to Manage Email Alerts
Low-dose norethandrolone during postinduction treatment significantly improved survival outcomes among elderly patients with newly diagnosed acute myeloid leukemia, according to a multicenter, phase 3, randomized open-label trial published in Journal of Clinical Oncology.
“Elderly patients with AML have a poor prognosis and innovative maintenance therapy could improve their outcomes,” Arnaud Pigneux, MD, University Hospital of Bordeaux, and colleagues wrote. “This study demonstrates that maintenance therapy with norethandrolone significantly improves survival in elderly patients with AML without increasing toxicity.”
More than 70% of patients with AML are aged older than 60 years at the time of diagnosis. Their lower tolerance to intensive chemotherapies and the presence of comorbidities has resulted in OS rarely exceeding 15% beyond 5 years from diagnosis.
“For this group of patients, improving the efficacy of postinduction chemotherapy and prolonging remission without increasing treatment-related mortality remains a challenge,” Pigneux and colleagues wrote.
Researchers of the Groupe Ouest Est d’Etude des Leucémies et Autres Maladies du Sang evaluated whether the addition of androgens — which are used in the treatment of aplastic anemia and have been shown to block the proliferation of AML cells — during postinduction treatment would improve outcomes among 330 elderly patients with AML de novo or secondary to chemotherapy or radiotherapy.
All patients received induction therapy with idarubicin (8 mg/m2 on days 1 to 5), cytarabine (100 mg/m2 on days 1 to 7), and lomustine (Gleostine, Corden Pharma; 200 mg/m2 on day 1). Patients in complete or partial remission received six reinduction courses.
Researchers then randomly assigned eligible patients to receive norethandrolone (10 or 20 mg per day according to body weight) for a 2-year maintenance therapy regimen (n = 162; median age, 70 years; 52% women) or no maintenance therapy (n = 163; median age, 70 years; 46% women).
Complete or partial remission occurred in 247 patients (76%), including 230 patients (70.7%) who achieved a complete response.
At the time of the analysis, median follow-up from the start of induction chemotherapy was 1.2 years for all patients and 4.6 years for surviving patients.
Among the patients who achieved a complete response, 31.2% in the maintenance therapy arm achieved 5-year DFS compared with 16.2% of patients in the no maintenance arm (P = .002).
More patients assigned maintenance also achieved 5-year EFS (21.5% vs. 12.9%) and 5-year OS (26.3% vs. 17.2%).
Norethandrolone improved outcomes regardless of prognosis factors; however, patients with baseline leukocytes greater than 30 x 109/L did not appear to benefit from maintenance.
“It may ... be hypothesized that long-term restoration of a balance controlling residual leukemic cells would be responsible for the observed positive effect of androgen supplementation,” the researchers wrote. “[This] would need to be tested in a future new prospective trial with norethandrolone or other more widely accessible androgens, together with an exploration of the cytogenetic/molecular subgroups of patients most likely to benefit from such an addition to therapy.
“Globally, however, these data suggest that for the nonnegligible population of elderly patients with AML with a white blood cell could count less than 30 x 109/L at diagnosis, the addition of androgens could become a valid cost-effective maintenance therapy.” – by Chuck Gormley
Disclosure: Pigneux and one other researcher report consultant/advisory roles with Amgen and Novartis.
Perspective
Back to Top
Abimbola Farinde
A diagnosis of acute myeloid leukemia can be devastating for any individual, but even more so for elderly patients. The survival rate among elderly patients with AML can be poor, and any available therapeutic option that can be used to improve outcomes is desired by both patients and health care professionals.
The use of androgens — particularly norethandrolone — may improve survival without causing significant toxic effects or treatment–related mortality in this vulnerable patient population. In addition, there is the potential that these findings may be applicable beyond elderly patients with AML and aid in the search for treatment options for other types of blood cancers. Additional studies also should be conducted in other patient populations with AML to determine if the same outcomes can be observed.
Ultimately, the decision to undergo this innovative therapy or any other must be evaluated on a case-by case-basis to determine if the benefits truly outweigh the possible risks. Future studies can potentially examine if any significant differences in survival outcomes emerged between patients who received 10 mg of norethandrolone vs. those who received 20-mg doses.
Disclosure: Farinde reports no relevant financial disclosures.
Click Here to Manage Email Alerts