Low-dose decitabine versus best supportive care in elderly patients with intermediate-or high-risk myelodysplastic syndrome (MDS) ineligible for intensive …
M Lübbert, S Suciu, L Baila, BH Rüter… - Journal of clinical …, 2011 - ascopubs.org
M Lübbert, S Suciu, L Baila, BH Rüter, U Platzbecker, A Giagounidis, D Selleslag, B Labar…
Journal of clinical oncology, 2011•ascopubs.orgPurpose To compare low-dose decitabine to best supportive care (BSC) in higher-risk
patients with myelodysplastic syndrome (MDS) age 60 years or older and ineligible for
intensive chemotherapy. Patients and Methods Two-hundred thirty-three patients (median
age, 70 years; range, 60 to 90 years) were enrolled; 53% had poor-risk cytogenetics, and
the median MDS duration at random assignment was 3 months. Primary end point was
overall survival (OS). Decitabine (15 mg/m2) was given intravenously over 4 hours three …
patients with myelodysplastic syndrome (MDS) age 60 years or older and ineligible for
intensive chemotherapy. Patients and Methods Two-hundred thirty-three patients (median
age, 70 years; range, 60 to 90 years) were enrolled; 53% had poor-risk cytogenetics, and
the median MDS duration at random assignment was 3 months. Primary end point was
overall survival (OS). Decitabine (15 mg/m2) was given intravenously over 4 hours three …
Purpose
To compare low-dose decitabine to best supportive care (BSC) in higher-risk patients with myelodysplastic syndrome (MDS) age 60 years or older and ineligible for intensive chemotherapy.
Patients and Methods
Two-hundred thirty-three patients (median age, 70 years; range, 60 to 90 years) were enrolled; 53% had poor-risk cytogenetics, and the median MDS duration at random assignment was 3 months. Primary end point was overall survival (OS). Decitabine (15 mg/m2) was given intravenously over 4 hours three times a day for 3 days in 6-week cycles.
Results
OS prolongation with decitabine versus BSC was not statistically significant (median OS, 10.1 v 8.5 months, respectively; hazard ratio [HR], 0.88; 95% CI, 0.66 to 1.17; two-sided, log-rank P = .38). Progression-free survival (PFS), but not acute myeloid leukemia (AML) –free survival (AMLFS), was 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; P = .004; median AMLFS, 8.8 v 6.1 months, respectively; HR, 0.85; 95% CI, 0.64 to 1.12; P = .24). AML transformation was significantly (P = .036) 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, respectively. Decitabine treatment was associated with improvements in patient-reported quality-of-life (QOL) parameters.
Conclusion
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.
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