title: Decitabine versus best supportive care in older patients with refractory anemia with excess blasts in transformation (RAEBt) - results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group (GMDSSG).
abstract: In the European Organisation for Research and Treatment of Cancer (EORTC)/GMDSSG phase III trial 06011, we compared decitabine (15 mg/m(2) every 8 h for 3 days) with best supportive care (BSC) in patients ≥60 years with myelodysplastic syndromes (MDS) by French-American-British (FAB) criteria. Here, we reinvestigate trial 06011 for the activity and efficacy specifically in patients with refractory anemia with excess blasts in transformation (RAEBt). Response rates in the decitabine arm (N = 40) were as follows: complete or partial remission, 15 %; hematologic improvement, 15 %; resistant disease, 30 %. RAEBt patients in the decitabine arm had longer progression-free survival (PFS; hazard ratio (HR) 0.30, 95 % confidence interval (CI) 0.18-0.51; median, 6.2 vs 2.8 months) and overall survival (OS; HR 0.68, 95 % CI 0.42-1.11; median, 8.0 vs 6.0 months) than in the BSC arm (N = 35). Censoring at allogeneic hematopoietic stem cell transplantation, the OS difference between the treatment groups increased, particularly among patients aged 60-74 years (HR 0.48, 95 % CI 0.26-0.89). After regrouping the study cohort according to World Health Organization (WHO) criteria, patients with acute myeloid leukemia (AML) (i.e., ≥20 % blasts) in the decitabine arm (N = 27) also had longer PFS than in the BSC arm (N = 23) (HR 0.46, 95 % CI 0.26-0.83; median, 6.2 vs 2.8 months). In conclusion, 3-day decitabine displays clinical activity and efficacy in MDS and/or AML with 5-30 % blood or 20-30 % marrow blasts.
authors.affiliation: Department of Medicine I, Medical Center-University of Freiburg, Freiburg, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Becker
authors.affiliation: EORTC Headquarters, Brussels, Belgium.
authors.forename: Stefan
authors.initials: S
authors.lastname: Suciu
authors.affiliation: Department of Medicine I, Medical Center-University of Freiburg, Freiburg, Germany.
authors.forename: Björn Hans
authors.initials: BH
authors.lastname: Rüter
authors.affiliation: Department of Internal Medicine I, University Carl Gustav Carus, Dresden, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Platzbecker
authors.affiliation: Department of Hematology, Oncology and Palliative Care, Marienhospital Düsseldorf, Düsseldorf, Germany.
authors.forename: Aristoteles
authors.initials: A
authors.lastname: Giagounidis
authors.affiliation: Department of Hematology, AZ St-Jan, Brugge, Belgium.
authors.forename: Dominik
authors.initials: D
authors.lastname: Selleslag
authors.affiliation: University Hospital Center Rebro, Zagreb, Croatia.
authors.forename: Boris
authors.initials: B
authors.lastname: Labar
authors.affiliation: Department of Hematology, Oncology and Clinical Immunology, University Hospital Düsseldorf, Düsseldorf, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Germing
authors.affiliation: Department of Hematology, Oncology and Immunology, Eberhard Karls University, Tübingen, Germany.
authors.forename: Helmut R
authors.initials: HR
authors.lastname: Salih
authors.affiliation: Radboud University Medical Center, Nijmegen, Netherlands.
authors.forename: Petra
authors.initials: P
authors.lastname: Muus
authors.affiliation: Department of Medicine II, DIAKO Bremen, Bremen, Germany.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Pflüger
authors.affiliation: Center for Human Genetics, University of Leuven, Leuven, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Hagemeijer
authors.affiliation: Institute of Pathology, University of Freiburg, Freiburg, Germany.
authors.forename: Hans-Eckart
authors.initials: HE
authors.lastname: Schaefer
authors.affiliation: EORTC Headquarters, Brussels, Belgium.
authors.forename: Valeria
authors.initials: V
authors.lastname: Fiaccadori
authors.affiliation: Centre Hospitalier Universitaire Sart-Tilman, Liège, Belgium.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Baron
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.affiliation: Department of Hematology and Oncology, St. Johannes Hospital, Duisburg, Germany.
authors.forename: Carlo
authors.initials: C
authors.lastname: Aul
authors.affiliation: Radboud University Medical Center, Nijmegen, Netherlands.
authors.forename: Theo
authors.initials: T
authors.lastname: de Witte
authors.affiliation: Department of Internal Medicine, Haga Ziekenhuis, The Hague, Netherlands.
authors.forename: Pierre W
authors.initials: PW
authors.lastname: Wijermans
authors.affiliation: Department of Medicine I, Medical Center-University of Freiburg, Freiburg, Germany. michael.luebbert@uniklinik-freiburg.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Lübbert
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000754:Anemia, Refractory, with Excess of Blasts / Q000401:mortality* / Q000628:therapy*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D001752:Blast Crisis / Q000401:mortality* / Q000628:therapy*; D000077209:Decitabine; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015996:Survival Rate
chemical_list: D000964:Antimetabolites, Antineoplastic; D000077209:Decitabine; D001374:Azacitidine
keywords: AML; Allogeneic transplantation; Epigenetic therapy; Leukemia; MDS; RAEBt