title: Phase I/II study of clofarabine, etoposide, and mitoxantrone in patients with refractory or relapsed acute leukemia.
abstract: BACKGROUND
  Clofarabine, a second-generation nucleoside analogue, was studied in combination with etoposide and mitoxantrone in acute leukemia.
  
  
  METHODS
  In the phase I portion of this study clofarabine was given 20 or 25 mg/m(2) daily for 5 days (Days 2-6) with etoposide 100 mg/m(2) from day 1 to 5 and mitoxantrone 8 mg/m(2) from day 1 to 3. The dose-limiting toxicity was myelosuppression, and dose level 1, with clofarabine 20 mg/m(2) daily for 5 days was identified as the phase 2 dose. In total, 22 patients with relapsed or refractory acute myeloid leukemia (n = 18) and acute lymphocytic leukemia (n = 4) were treated.
  
  
  RESULTS
  Five of 22 patients (23%) achieved complete response (CR), and 3 (13%) achieved CR with incomplete platelet recovery; an overall response rate of 36%. Median overall survival was 167 days (range, 22-1327 days). For 2 patients this regimen represented an effective bridge to allogeneic stem cell transplantation.
  
  
  CONCLUSIONS
  Clofarabine in combination with etoposide and mitoxantrone is tolerable and shows significant activity in relapsed and refractory acute leukemia in adults.
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Kamal K S
authors.initials: KK
authors.lastname: Abbi
authors.affiliation: Penn State College of Medicine, Hershey, PA.
authors.forename: Witold
authors.initials: W
authors.lastname: Rybka
authors.affiliation: Penn State College of Medicine, Hershey, PA.
authors.forename: W Christopher
authors.initials: WC
authors.lastname: Ehmann
authors.affiliation: Penn State College of Medicine, Hershey, PA. Electronic address: dclaxton@hmc.psu.edu.
authors.forename: David F
authors.initials: DF
authors.lastname: Claxton
mesh_terms: D000227:Adenine Nucleotides / Q000008:administration & dosage; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001087:Arabinonucleosides / Q000008:administration & dosage; D000077866:Clofarabine; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D009367:Neoplasm Staging; D012008:Recurrence; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D000227:Adenine Nucleotides; D001087:Arabinonucleosides; D005047:Etoposide; D000077866:Clofarabine; D008942:Mitoxantrone
keywords: Acute myeloid leukemia; Adult; Clofarabine; Refractory; Relapse