Low-dose decitabine versus best supportive care in elderly patients with intermediate- or high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy: Final results of the randomized phase III study of the European Organisation for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group Full Text
Journal of Clinical Oncology, 04/14/2011
Clinical Article
Lübbert M et al. – Decitabine administered in 6-week cycles is active in older patients with higher-risk MDS, resulting in improvements of OS and AMLFS (nonsignificant), of PFS and AML transformation (significant), and of QOL. Short MDS duration was an independent adverse prognosticator.
Methods- 233 patients (median age, 70 years; range, 60 to 90 years) enrolled; 53% had poor-risk cytogenetics, and median MDS duration at random assignment 3 months
- Primary end point OS
- Decitabine (15 mg/m2) given intravenously over 4 hours TID for 3 days in 6-week cycles
- OS prolongation with decitabine versus BSC not statistically significant (median OS, 10.1 v 8.5 months, respectively; HR, 0.88; 95% CI, 0.66 to 1.17; 2-sided)
- PFS, but not AML – free survival (AMLFS), significantly prolonged with decitabine versus BSC (median PFS, 6.6 v 3.0 months, respectively; HR, 0.68; 95% CI, 0.52 to 0.88; median AMLFS, 8.8 v 6.1 months, respectively; HR, 0.85; 95% CI, 0.64 to 1.12)
- AML transformation significantly reduced at 1 year (from 33% with BSC to 22% with decitabine)
- Multivariate analyses indicated that patients with short MDS duration had worse outcomes
- Best responses with decitabine versus BSC, respectively, were as follows: complete response (13% v 0%), partial response (6% v 0%), hematologic improvement (15% v 2%), stable disease (14% v 22%), progressive disease (29% v 68%), hypoplasia (14% v 0%), and inevaluable (8% v 8%)
- Grade 3 to 4 febrile neutropenia occurred in 25% of patients on decitabine versus 7% of patients on BSC; grade 3 to 4 infections occurred in 57% and 52% of patients on decitabine and BSC
- Decitabine treatment associated with improvements in patient-reported QOL parameters
