title: Randomized open-label phase II study of decitabine in patients with low- or intermediate-risk myelodysplastic syndromes.
abstract: OBJECTIVE
  This open-label, randomized phase II trial assessed efficacy and tolerability of two low-dose regimens of subcutaneous (SC) decitabine in patients with low- or intermediate-1-risk myelodysplastic syndrome (MDS).
  
  
  METHODS
  Patients received decitabine 20 mg/m(2) SC per day for 3 consecutive days on days 1, 2, and 3 every 28 days (schedule A) or 20 mg/m(2) SC per day once every 7 days on days 1, 8, and 15 every 28 days (schedule B) for up to 1 year. Primary efficacy end point was overall improvement rate (OIR: complete remission [CR], partial remission [PR], marrow CR [mCR], or hematologic improvement [HI]). Secondary end points were HI, transfusion independence, cytogenetic response, overall survival (OS), and time to acute myeloid leukemia or death.
  
  
  RESULTS
  Efficacy and safety populations were identical: schedule A, n = 43; schedule B, n = 22. Median time from MDS diagnosis to treatment was 3.6 months; 89% had de novo MDS. The trial was terminated early on achievement of protocol-defined OIR superiority of schedule A over schedule B; OIR was 23% for schedule A (seven CRs, three HIs) and 23% for schedule B (one mCR, one PR, three HIs). No differences were observed in secondary end points. Median OS was not reached; approximately 70% of patients were alive at 500 days. Patients in schedule A (67%) and schedule B (59%) were RBC/platelet independent on study. The most frequent drug-related adverse events overall were neutropenia (28% v 36%), anemia (23% v 18%), and thrombocytopenia (16% v 32%).
  
  
  CONCLUSIONS
  In this phase II study, low-dose decitabine showed promising results in patients with low- or intermediate-1-risk MDS.
authors.affiliation: The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA. ggarciam@mdanderson.org
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Zeev
authors.initials: Z
authors.lastname: Estrov
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.forename: Sirisha
authors.initials: S
authors.lastname: Maddipoti
authors.forename: Lucy A
authors.initials: LA
authors.lastname: Godley
authors.forename: Nashat
authors.initials: N
authors.lastname: Gabrail
authors.forename: Jesus G
authors.initials: JG
authors.lastname: Berdeja
authors.forename: Ahmed
authors.initials: A
authors.lastname: Nadeem
authors.forename: Laurent
authors.initials: L
authors.lastname: Kassalow
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D001374:Azacitidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077209:Decitabine; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D053208:Kaplan-Meier Estimate; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012720:Severity of Illness Index; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D000077209:Decitabine; D001374:Azacitidine