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Leuk Res. 2013 Aug;37(8):980-4. doi: 10.1016/j.leukres.2013.04.019. Epub 2013 May 6.

Epigenetic action of decitabine (5-aza-2'-deoxycytidine) is more effective against acute myeloid leukemia than cytotoxic action of cytarabine (ARA-C).

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1
Département de pharmacologie, Université de Montréal, Canada. richard.l.momparler@umontreal.ca

Abstract

Treatment of elderly patients with acute myeloid leukemia (AML) with standard cytarabine (ARA-C) chemotherapy can achieve some complete responses (CR), but the median overall survival is less than one year. New approaches should be investigated. The inhibitor of DNA methylation, 5-aza-2'-deoxycytidine (decitabine, DAC), shows effectiveness in these patients, but was not approved by the US Federal Drug Administration. This decision was based on a clinical trial where DAC showed a median survival of 7.0 months as compared to standard ARA-C therapy or supportive care of 5.0 months. However, the difference was not statistically significant. Preclinical data indicate that DAC is much more effective against human AML than ARA-C. The key question is should these preclinical data also be used in the evaluation of new drugs for the clinical treatment of AML? The delayed epigenetic action of DAC is very different than the acute cytotoxic action of ARA-C and should be taken into account in the design clinical trials and evaluation of the response.

PMID:
23660386
DOI:
10.1016/j.leukres.2013.04.019
[Indexed for MEDLINE]

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