title: Further analysis of trials with azacitidine in patients with myelodysplastic syndrome: studies 8421, 8921, and 9221 by the Cancer and Leukemia Group B.
abstract: OBJECTIVE
  Within the last two decades, a new understanding of the biology of myelodysplastic syndrome (MDS) has developed. With this understanding, new classification systems, such as the WHO diagnostic criteria, and the International Prognostic Scoring System and response criteria guidelines reported by the International Working Group (IWG) have been developed. We report the combined results of three previously reported clinical trials (n = 309) with azacitidine using the WHO classification system for MDS and acute myeloid leukemia (AML) and IWG criteria for response.
  
  
  METHODS
  Data from three sequential Cancer and Leukemia Group B trials with azacitidine were recollected and reanalyzed as part of the New Drug Application process. The trials were conducted with either intravenous or subcutaneous azacitidine (75 mg/m2/d for 7 days every 28 days).
  
  
  RESULTS
  Complete remissions were seen in 10% to 17% of azacitidine-treated patients; partial remissions were rare; 23% to 36% of patients had hematologic improvement (HI). The median number of cycles to first response was three, and 90% of responses were seen by cycle 6. Using current WHO criteria, 103 patients had AML at baseline; 35% to 48% had HI or better responses. The median survival time for the 27 AML patients randomly assigned to azacitidine was 19.3 months compared with 12.9 months for the 25 patients assigned to observation. Furthermore, azacitidine did not increase the rate of infection or bleeding above the rate caused by underlying disease.
  
  
  CONCLUSIONS
  Azacitidine provides important clinical benefits for patients with high-risk MDS.
authors.affiliation: Division of Hematology/Oncology, Mount Sinai School of Medicine, New York, NY 10029, USA. lewis.silverman@mssm.edu
authors.forename: Lewis R
authors.initials: LR
authors.lastname: Silverman
authors.forename: David R
authors.initials: DR
authors.lastname: McKenzie
authors.forename: Bercedis L
authors.initials: BL
authors.lastname: Peterson
authors.forename: James F
authors.initials: JF
authors.lastname: Holland
authors.forename: Jay T
authors.initials: JT
authors.lastname: Backstrom
authors.forename: C L
authors.initials: CL
authors.lastname: Beach
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001374:Azacitidine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001803:Blood Transfusion / Q000706:statistics & numerical data*; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D015337:Multicenter Studies as Topic; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000188:drug therapy* / Q000628:therapy; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine