European development of clofarabine as treatment for older patients with acute myeloid leukemia considered unsuitable for intensive chemotherapy.
OBJECTIVE
Treatment options for older patients with acute myeloid leukemia (AML) who are not considered suitable for intensive chemotherapy are limited. We assessed the second-generation purine nucleoside analog, clofarabine, in two similar phase II studies in this group of patients.


METHODS
Two consecutive studies, UWCM-001 and BIOV-121, recruited untreated older patients with AML to receive up to four or six 5-day courses of clofarabine. Patients in UWCM-001 were either older than 70 years or 60 to 69 years of age with poor performance status (WHO > 2) or with cardiac comorbidity. Patients in BIOV-121 were >or= 65 years of age and deemed unsuitable for intensive chemotherapy.


RESULTS
A total of 106 patients were treated in the two monotherapy studies. Median age was 71 years (range, 60 to 84 years), 30% had adverse-risk cytogenetics, and 36% had a WHO performance score >or= 2. Forty-eight percent had a complete response (32% complete remission, 16% complete remission with incomplete peripheral blood count recovery), and 18% died within 30 days. Interestingly, response and overall survival were not inferior in the adverse cytogenetic risk group. The safety profile of clofarabine in these elderly patients with AML who were unsuitable for intensive chemotherapy was manageable and typical of a cytotoxic agent in patients with acute leukemia. Patients had similar prognostic characteristics to matched patients treated with low-dose cytarabine in the United Kingdom AML14 trial, but had significantly superior response and overall survival.


CONCLUSIONS
Clofarabine is active and generally well tolerated in this patient group. It is worthy of further evaluation in comparative trials and might be of particular use in patients with adverse cytogenetics.
Burnett
Alan K
AK
Department of Haematology, Cardiff University School of Medicine, Cardiff CF14 4XN, United Kingdom. burnettak@cardiff.ac.uk
Russell
Nigel H
NH
Kell
Jonathan
J
Dennis
Michael
M
Milligan
Donald
D
Paolini
Stefania
S
Yin
John
J
Culligan
Dominic
D
Johnston
Peter
P
Murphy
John
J
McMullin
Mary-Frances
MF
Hunter
Ann
A
Das-Gupta
Emma
E
Clark
Richard
R
Carr
Robert
R
Hills
Robert K
RK
D000227:Adenine Nucleotides / Q000009:adverse effects / Q000627:therapeutic use*; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001087:Arabinonucleosides / Q000009:adverse effects / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D000077866:Clofarabine; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007558:Italy; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D016017:Odds Ratio; D018579:Patient Selection; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D006113:United Kingdom
D000227:Adenine Nucleotides; D000970:Antineoplastic Agents; D001087:Arabinonucleosides; D000077866:Clofarabine