Objective: To review the literature evaluating the efficacy and tolerability of clofarabine, a second-generation purine nucleoside analogue, for the treatment of previously untreated acute myeloid leukemia (AML) in older adults.
Data source: A literature search of the PubMed database (1972-October 2011) using the search terms clofarabine and acute myeloid leukemia was performed.
Study selection and data extraction: All relevant English-language articles were reviewed, and clinical trials with patients aged 50 years or older who were newly diagnosed with AML were included.
Data synthesis: Two studies evaluating clofarabine as monotherapy and 2 studies evaluating clofarabine in combination with cytarabine were reviewed. Clofarabine demonstrated activity in older adults with previously untreated AML. Response rates and median overall survival (OS) for patients receiving clofarabine were similar to those reported for conventional intensive chemotherapy regimens. Responses to the 2 types of treatment remained similar in the presence of unfavorable prognostic factors, such as secondary AML or adverse cytogenetics. Although clofarabine was associated with a lower induction mortality rate versus intensive chemotherapy regimens, a significant percentage of patients experienced severe complications, including sepsis. Compared to single-agent clofarabine, response rates and median OS were higher for clofarabine combined with cytarabine.
Conclusions: Based on published data, adverse effect profiles, and cost, clofarabine may be an appropriate alternative to intensive chemotherapy regimens in certain subsets of older patients with newly diagnosed AML. These include patients with a baseline decreased performance status or history of cardiovascular disease who may not tolerate anthracyclines, which are typically a component of most intensive chemotherapy regimens. Additional randomized controlled trials are needed to directly compare the efficacy of clofarabine with that of intensive chemotherapy regimens and to evaluate the potential benefit of combining clofarabine with cytarabine.