title: Clofarabine with high dose cytarabine and granulocyte colony-stimulating factor (G-CSF) priming for relapsed and refractory acute myeloid leukaemia.
abstract: This phase I/II study was conducted to determine the maximum tolerated dose, toxicity, and efficacy of clofarabine in combination with high dose cytarabine and granulocyte colony-stimulating factor (G-CSF) priming (GCLAC), in the treatment of patients with relapsed or refractory acute myeloid leukaemia (AML). Dose escalation of clofarabine occurred without dose-limiting toxicity, so most patients were treated at the maximum dose, 25 mg/m(2) per day with cytarabine 2 g/m(2) per day, each for 5 d, and G-CSF 5 μg/kg, beginning the day before chemotherapy and continuing daily until neutrophil recovery. The complete remission (CR) rate among the 46 evaluable patients was 46% (95% confidence interval [CI] 31-61%) and the CR + CR but with a platelet count <100 × 10(9)/l rate was 61% (95% CI 45-75%). Multivariate analysis showed that responses to GCLAC were independent of age, cytogenetic risk category, and number of prior salvage regimens. GCLAC is highly active in relapsed and refractory AML and warrants prospective comparison to other regimens, as well as study in untreated patients.
authors.affiliation: Division of Hematology and Medical Oncology, University of Washington, Seattle, WA 98109, USA. pbecker@u.washington.edu
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Becker
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Petersdorf
authors.forename: Barry
authors.initials: B
authors.lastname: Storer
authors.forename: Sherry
authors.initials: S
authors.lastname: Pierce
authors.forename: Jianqin
authors.initials: J
authors.lastname: Shan
authors.forename: Paul C
authors.initials: PC
authors.lastname: Hendrie
authors.forename: John M
authors.initials: JM
authors.lastname: Pagel
authors.forename: Andrei R
authors.initials: AR
authors.lastname: Shustov
authors.forename: Derek L
authors.initials: DL
authors.lastname: Stirewalt
authors.forename: Stephan
authors.initials: S
authors.lastname: Faderl
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Harrington
authors.forename: Elihu H
authors.initials: EH
authors.lastname: Estey
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007239:Infections / Q000209:etiology; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D016016:Proportional Hazards Models; D012008:Recurrence; D012074:Remission Induction; D012306:Risk; D016879:Salvage Therapy; D055815:Young Adult
chemical_list: D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor