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
| Autor: | Arnold Ganser, Theo de Witte, Liliana Baila, Stefan Suciu, Petra Muus, Michael Lübbert, Carlo Aul, Corneel Coens, Björn Rüter, Anne Hagemeijer, Karl-Heinz Pflüger, Aristoteles Giagounidis, F. Beeldens, Boris Labar, Dominik Selleslag, Ulrich Germing, Helmut R. Salih, Pierre W. Wijermans, Hans E. Schaefer, Uwe Platzbecker |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
Antimetabolites Antineoplastic Cancer Research medicine.medical_specialty Palliative care medicine.medical_treatment Azacitidine Decitabine Disease-Free Survival Translational research [ONCOL 3] Internal medicine medicine Clinical endpoint Humans Aged Aged 80 and over Chemotherapy business.industry Myelodysplastic syndromes Palliative Care Hazard ratio Translational research Immune Regulation [ONCOL 3] Middle Aged medicine.disease Surgery Treatment Outcome decitabine elderly high risk MDS Oncology Myelodysplastic Syndromes Quality of Life Cytarabine Female business medicine.drug |
| Zdroj: | Journal of Clinical Oncology, 29, 15, pp. 1987-96 Journal of Clinical Oncology, 29, 1987-96 |
| ISSN: | 0732-183X |
| DOI: | 10.1200/jco.2010.30.9245 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|