title: 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.
abstract: OBJECTIVE
  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.
  
  
  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/m(2)) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Albert Ludwigs University, Freiburg, Germany. michael.luebbert@uniklinik-freiburg.de
authors.forename: Michael
authors.initials: M
authors.lastname: Lübbert
authors.forename: Stefan
authors.initials: S
authors.lastname: Suciu
authors.forename: Liliana
authors.initials: L
authors.lastname: Baila
authors.forename: Björn Hans
authors.initials: BH
authors.lastname: Rüter
authors.forename: Uwe
authors.initials: U
authors.lastname: Platzbecker
authors.forename: Aristoteles
authors.initials: A
authors.lastname: Giagounidis
authors.forename: Dominik
authors.initials: D
authors.lastname: Selleslag
authors.forename: Boris
authors.initials: B
authors.lastname: Labar
authors.forename: Ulrich
authors.initials: U
authors.lastname: Germing
authors.forename: Helmut R
authors.initials: HR
authors.lastname: Salih
authors.forename: Filip
authors.initials: F
authors.lastname: Beeldens
authors.forename: Petra
authors.initials: P
authors.lastname: Muus
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Pflüger
authors.forename: Corneel
authors.initials: C
authors.lastname: Coens
authors.forename: Anne
authors.initials: A
authors.lastname: Hagemeijer
authors.forename: Hans
authors.initials: H
authors.lastname: Eckart Schaefer
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.forename: Carlo
authors.initials: C
authors.lastname: Aul
authors.forename: Theo
authors.initials: T
authors.lastname: de Witte
authors.forename: Pierre W
authors.initials: PW
authors.lastname: Wijermans
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D001374:Azacitidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077209:Decitabine; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D010166:Palliative Care; D011788:Quality of Life; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D000077209:Decitabine; D001374:Azacitidine