Clofarabine and cytarabine combination as induction therapy for acute myeloid leukemia (AML) in patients 50 years of age or older.
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.
Faderl
Stefan
S
Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX 77230-1402, USA. sfaderl@mdanderson.org
Verstovsek
Srdan
S
Cortes
Jorge
J
Ravandi
Farhad
F
Beran
Miloslav
M
Garcia-Manero
Guillermo
G
Ferrajoli
Alessandra
A
Estrov
Zeev
Z
O'Brien
Susan
S
Koller
Charles
C
Giles
Francis J
FJ
Wierda
William
W
Kwari
Monica
M
Kantarjian
Hagop M
HM
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
D000227:Adenine Nucleotides; D001087:Arabinonucleosides; D003561:Cytarabine; D000077866:Clofarabine