title: Decitabine can be safely reduced after achievement of best objective response in patients with myelodysplastic syndrome.
abstract: BACKGROUND
  Decitabine is standard therapy in patients with myelodysplastic syndrome (MDS). Current recommendations suggest a dose of 20 mg/m(2) intravenously (IV) daily for 5 days every 4 weeks. However, this therapy is associated with frequent grade 3/4 hematologic toxicity, requiring dose delays and/or dose reductions (DD/DR).
  
  
  RESULTS
  We investigated the outcomes of 122 patients with MDS who had DD/DR of frontline decitabine therapy. Sixty-five patients (53%) had DR by at least 25% or DD (defined as a delay beyond 5 weeks between cycles). Thirty-five patients (29%) underwent DD/DR after achieving best objective response, 30 patients (25%) underwent DD/DR before best objective response, and 57 (54%) patients had no DD/DR. There was a trend for more durable responses in favor of patients requiring DD/DR after the achievement of best objective response (median not reached) (P = .161). Overall survival rates were significantly higher for patients who had DD/DR after best objective response compared with those who had DD/DR before best objective response or those with no DD/DR (30 vs. 22 vs. 11 months, respectively; P < .001). Progression-free survival (PFS) rates also trended higher for those with DD/DR after best objective response (median not reached) compared with those who required DD/DR before best objective response (median of 15 months) (P = .285).
  
  
  CONCLUSIONS
  DD/DR may be safely accomplished once the patient has achieved best objective response (preferably complete remission [CR]) without impacting outcome. Prospective evaluation of an approach conceived of a loading dose for induction of a best objective response followed by a maintenance schedule is to be considered.
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors: Hady
authors: H
authors: Ghanem
authors: A Megan
authors: AM
authors: Cornelison
authors: Guillermo
authors: G
authors: Garcia-Manero
authors: Hagop
authors: H
authors: Kantarjian
authors: Farhad
authors: F
authors: Ravandi
authors: Tapan
authors: T
authors: Kadia
authors: Jorge
authors: J
authors: Cortes
authors: Susan
authors: S
authors: O'Brien
authors: Mark
authors: M
authors: Brandt
authors: Gautam
authors: G
authors: Borthakur
authors: Elias
authors: E
authors: Jabbour
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; 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; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D012074:Remission Induction; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D000077209:Decitabine; D001374:Azacitidine
keywords: Decitabine; Dose delay; Dose reduction; Myelodysplastic syndrome
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