title: A randomized study of 2 dose levels of intravenous clofarabine in the treatment of patients with higher-risk myelodysplastic syndrome.
abstract: BACKGROUND
  Clofarabine is a nucleoside analog with activity in myeloid malignancies. Experience in myelodysplastic syndrome (MDS) is limited.
  
  
  METHODS
  The goal of this study was to evaluate the activity and safety of 2 different doses (15 mg/m(2) vs 30 mg/m(2) daily × 5 days) of intravenous clofarabine in patients with higher-risk MDS. Fifty-eight patients with a median age of 68 years (range, 25-89) including 15 patients (28%) with secondary MDS and 35 patients (60%) who received prior DNA methyltransferase (DNMT) inhibitors were adaptively randomized between the 2 dose cohorts.
  
  
  RESULTS
  The overall response rate (ORR; based on a modification of International Working Group criteria) was 36% including 26% with complete remission (CR) (ORR, 41% at 15 mg/m(2) and 29% at 30 mg/m(2)). Responses were lower in patients who failed DNMT inhibitors (ORR, 17%; CR rate, 14%). The 8-week mortality rate was 19%. Median survival was 7.4 months for all patients, 13.4 months for responders, and 21.7 months for complete responders. Some adverse events, particularly hepatic and renal, were more severe (grade >2) in patients randomized to 30 mg/m(2) of clofarabine. Myelosuppression and infectious complications were frequent.
  
  
  CONCLUSIONS
  Both the lower and higher doses of clofarabine have comparable clinical activity, but the lower dose appeared less toxic. If these results are confirmed, lower doses of clofarabine, possibly in alternative schedules, should be pursued.
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas 77230-1402, USA. sfaderl@mdanderson.org
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.forename: Zeev
authors.initials: Z
authors.lastname: Estrov
authors.forename: Varsha
authors.initials: V
authors.lastname: Gandhi
authors.forename: Anna L
authors.initials: AL
authors.lastname: Byrd
authors.forename: Monica
authors.initials: M
authors.lastname: Kwari
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
mesh_terms: D000227:Adenine Nucleotides / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001087:Arabinonucleosides / Q000008:administration & dosage*; D000077866:Clofarabine; D015331:Cohort Studies; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000401:mortality*; D012074:Remission Induction; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000227:Adenine Nucleotides; D000970:Antineoplastic Agents; D001087:Arabinonucleosides; D000077866:Clofarabine