Hagop M. Kantarjian, MD
Decitabine produced a higher response rate than standard therapies in older patients with newly diagnosed acute myeloid leukemia (AML) without major differences in safety, according to the results of an open-label, phase III study. The drug is an azanucleoside DNA methyltransferase inhibitor that is approved under the trade name Dacogen for patients with previously treated and untreated de novo and secondary myelodysplastic syndromes.
Hagop M. Kantarjian, MD, chairman of the Leukemia Department at the University of Texas MD Anderson Cancer Center in Houston, and associates elsewhere randomized 485 patients with AML 1:1 to receive 20 mg/m2 of decitabine per day as a 1-hour intravenous infusion for 5 consecutive days every 4 weeks or “treatment choice.” Individuals assigned to the treatment choice arm indicated, with advice from their physician, their preferred treatment: either supportive care intended to maximize their quality of life or 20 mg/m2
of cytarabine per day as a subcutaneous injection for 10 consecutive days every 4 weeks. Supportive care and low-dose cytarabine are the most common AML treatments.
Study participants were aged ≥65 years and had de novo or secondary AML with poor- or intermediate-risk cytogenetics. The primary endpoint was overall survival (OS).
At the study’s 2009 cutoff, there was a nonsignificant but favorable trend toward an increased median OS with decitabine (7.7 months; 95% CI, 6.2-9.2 months) compared with treatment choice (5.0 months; 95% CI, 4.3-6.3 months). The estimated hazard ratio for death was 0.85 (95% CI, 0.69-1.04).
Also at the 2009 cutoff, the complete remission (CR) rate plus the CR rate without platelet recovery (CRp) was significantly higher in the decitabine group versus the treatment choice arm (17.8% vs 7.8%, respectively; P
An unplanned analysis based on mature data obtained at the 2010 cutoff showed that the OS difference favoring decitabine became significant (nominal P
Decitabine was well tolerated. The most common drug-related adverse events with decitabine were thrombocytopenia and neutropenia. Also, the incidence and severity of side effects that prompted withdrawal from treatment or death were similar between arms despite a longer treatment duration with decitabine.
The authors acknowledged that the study’s open-label design was a limitation. However, they explained that the open-label design was needed to compare the optimal regimen of intravenous decitabine with the conventional subcutaneous cytarabine regimen.
Acute myeloid leukemia is a common adult leukemia, with approximately 12,330 new cases diagnosed each year in the United States, the researchers wrote. While the disease is more common in elderly patients, treatment choices in this group are limited, especially in individuals with poor performance status and comorbidities. Several professional cancer societies recently added low-intensity cytarabine, 5-azacytidine, and decitabine to their AML treatment recommendations.
Kantarjian HM, Thomas XG, Dmoszynska A, et al. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012;30(21):2670-2677.