title: Clofarabine and cytarabine combination as induction therapy for acute myeloid leukemia (AML) in patients 50 years of age or older.
abstract: Outcome of patients with acute myeloid leukemia (AML) who are older than 60 years of age remains unsatisfactory, with low remission rates and poor overall survival. We have previously established the activity of clofarabine plus cytarabine in AML relapse. We have now conducted a phase 2 study of clofarabine plus cytarabine in patients aged 50 years or older with previously untreated AML. Clofarabine was given at 40 mg/m2 as a 1-hour intravenous infusion for 5 days (days 2 to 6) followed 4 hours later by cytarabine at 1 g/m2/d as a 2-hour intravenous infusion for 5 days (days 1 to 5). Of 60 patients, 29 (48%) had secondary AML, 30 (50%) had abnormal karyotypes (monosomy 5 and/or 7 in 15 [25%]), and 11 (21%) showed FLT3 abnormalities. The overall response (OR) rate was 60% (52% CR, 8% CRp). Four patients (7%) died during induction. Adverse events were mainly grade 2 or lower and included diarrhea, nausea, vomiting, mucositis, skin reactions, liver test abnormalities, and infusion-related facial flushing and headaches. Myelosuppression was common. Clofarabine plus cytarabine has activity in adult AML, achieving a good CR rate. However, survival does not appear to be improved compared with other regimens. Modifications of this combination in AML therapy of older patients warrant further evaluation.
authors.affiliation: Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX 77230-1402, USA. sfaderl@mdanderson.org
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Miloslav
authors.initials: M
authors.lastname: Beran
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferrajoli
authors.forename: Zeev
authors.initials: Z
authors.lastname: Estrov
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Charles
authors.initials: C
authors.lastname: Koller
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
authors.forename: William
authors.initials: W
authors.lastname: Wierda
authors.forename: Monica
authors.initials: M
authors.lastname: Kwari
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
mesh_terms: D000208:Acute Disease; D000227:Adenine Nucleotides / Q000008:administration & dosage* / Q000009:adverse effects; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001087:Arabinonucleosides / Q000008:administration & dosage* / Q000009:adverse effects; D002869:Chromosome Aberrations; D000077866:Clofarabine; D003561:Cytarabine / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D006801:Humans; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000188:drug therapy*; D008875:Middle Aged; D012074:Remission Induction; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000227:Adenine Nucleotides; D001087:Arabinonucleosides; D003561:Cytarabine; D000077866:Clofarabine