title: European development of clofarabine as treatment for older patients with acute myeloid leukemia considered unsuitable for intensive chemotherapy.
abstract: OBJECTIVE
  Treatment options for older patients with acute myeloid leukemia (AML) who are not considered suitable for intensive chemotherapy are limited. We assessed the second-generation purine nucleoside analog, clofarabine, in two similar phase II studies in this group of patients.
  
  
  METHODS
  Two consecutive studies, UWCM-001 and BIOV-121, recruited untreated older patients with AML to receive up to four or six 5-day courses of clofarabine. Patients in UWCM-001 were either older than 70 years or 60 to 69 years of age with poor performance status (WHO > 2) or with cardiac comorbidity. Patients in BIOV-121 were >or= 65 years of age and deemed unsuitable for intensive chemotherapy.
  
  
  RESULTS
  A total of 106 patients were treated in the two monotherapy studies. Median age was 71 years (range, 60 to 84 years), 30% had adverse-risk cytogenetics, and 36% had a WHO performance score >or= 2. Forty-eight percent had a complete response (32% complete remission, 16% complete remission with incomplete peripheral blood count recovery), and 18% died within 30 days. Interestingly, response and overall survival were not inferior in the adverse cytogenetic risk group. The safety profile of clofarabine in these elderly patients with AML who were unsuitable for intensive chemotherapy was manageable and typical of a cytotoxic agent in patients with acute leukemia. Patients had similar prognostic characteristics to matched patients treated with low-dose cytarabine in the United Kingdom AML14 trial, but had significantly superior response and overall survival.
  
  
  CONCLUSIONS
  Clofarabine is active and generally well tolerated in this patient group. It is worthy of further evaluation in comparative trials and might be of particular use in patients with adverse cytogenetics.
authors.affiliation: Department of Haematology, Cardiff University School of Medicine, Cardiff CF14 4XN, United Kingdom. burnettak@cardiff.ac.uk
authors.forename: Alan K
authors.initials: AK
authors.lastname: Burnett
authors.forename: Nigel H
authors.initials: NH
authors.lastname: Russell
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kell
authors.forename: Michael
authors.initials: M
authors.lastname: Dennis
authors.forename: Donald
authors.initials: D
authors.lastname: Milligan
authors.forename: Stefania
authors.initials: S
authors.lastname: Paolini
authors.forename: John
authors.initials: J
authors.lastname: Yin
authors.forename: Dominic
authors.initials: D
authors.lastname: Culligan
authors.forename: Peter
authors.initials: P
authors.lastname: Johnston
authors.forename: John
authors.initials: J
authors.lastname: Murphy
authors.forename: Mary-Frances
authors.initials: MF
authors.lastname: McMullin
authors.forename: Ann
authors.initials: A
authors.lastname: Hunter
authors.forename: Emma
authors.initials: E
authors.lastname: Das-Gupta
authors.forename: Richard
authors.initials: R
authors.lastname: Clark
authors.forename: Robert
authors.initials: R
authors.lastname: Carr
authors.forename: Robert K
authors.initials: RK
authors.lastname: Hills
mesh_terms: D000227:Adenine Nucleotides / Q000009:adverse effects / Q000627:therapeutic use*; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001087:Arabinonucleosides / Q000009:adverse effects / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D000077866:Clofarabine; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007558:Italy; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D016017:Odds Ratio; D018579:Patient Selection; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D006113:United Kingdom
chemical_list: D000227:Adenine Nucleotides; D000970:Antineoplastic Agents; D001087:Arabinonucleosides; D000077866:Clofarabine