title: Report of a phase II study of clofarabine and cytarabine in de novo and relapsed and refractory AML patients and in selected elderly patients at high risk for anthracycline toxicity.
abstract: OBJECTIVE
  To determine the efficacy and safety of clofarabine and cytarabine (Ara-C) in adult patients with relapsed or refractory acute myeloid leukemia (AML) and in elderly patients with untreated AML and heart disease.
  
  
  METHODS
  Patients with relapsed/refractory AML and older patients for whom there was a concern over toxicity from additional anthracyclines received 5 days of clofarabine, 40 mg/m(2) per day i.v. over 1 hour, followed 4 hours later by Ara-C, 1,000 mg/m(2) per day i.v. over 2 hours.
  
  
  RESULTS
  Thirty patients were enrolled. The median age was 67 years (range, 38-82 years) and 18 (60%) had received at least one prior therapy. Eleven (37%) patients had a history of cardiovascular disease and were considered to be at high risk for anthracycline toxicity. High-risk cytogenetic abnormalities were present in 14 (47%) patients. The overall response rate (complete remission [CR] plus partial remission) was 53%, including a CR in 14 patients (47%). Responses were observed in all cytogenetic risk groups and in patients who had received up to five prior therapies. The median disease-free survival interval was 9.5 months. The 30-day mortality rate was 20% (de novo AML, 8%; relapsed/refractory AML, 28%). Of the 14 patients achieving a CR, half were able to proceed to curative hematopoietic stem cell transplantation.
  
  
  CONCLUSIONS
  Clofarabine in combination with Ara-C is effective in both untreated and previously treated patients with AML. In addition, it represents a useful remission induction strategy to serve as a bridge to transplantation in older patients with AML.
authors.affiliation: Texas Oncology PA, Dallas, Texas, USA. edwarda@baylorhealth.edu
authors.forename: Edward
authors.initials: E
authors.lastname: Agura
authors.forename: Barry
authors.initials: B
authors.lastname: Cooper
authors.forename: Houston
authors.initials: H
authors.lastname: Holmes
authors.forename: Estil
authors.initials: E
authors.lastname: Vance
authors.forename: Robert Brian
authors.initials: RB
authors.lastname: Berryman
authors.forename: Christopher
authors.initials: C
authors.lastname: Maisel
authors.forename: Sandy
authors.initials: S
authors.lastname: Li
authors.forename: Giovanna
authors.initials: G
authors.lastname: Saracino
authors.forename: Mirjana
authors.initials: M
authors.lastname: Tadic-Ovcina
authors.forename: Joseph
authors.initials: J
authors.lastname: Fay
mesh_terms: D000227:Adenine Nucleotides / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001087:Arabinonucleosides / Q000008:administration & dosage*; D000077866:Clofarabine; D003561:Cytarabine / Q000008:administration & dosage*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D018579:Patient Selection; D012008:Recurrence; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000227:Adenine Nucleotides; D018943:Anthracyclines; D001087:Arabinonucleosides; D003561:Cytarabine; D000077866:Clofarabine