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Why Levamisole Appears to Improve the Efficacy of 5-FU

Why Levamisole Appears to Improve the Efficacy of 5-FU

British researchers reporting in a recent issue of the Journal of the National Cancer Institute offer a study-based explanation of why levamisole and fluorouracil (5-FU), used together, can lengthen survival for certain colon cancer patients, while neither drug alone has consistently been shown to make a difference.

The combination of these two drugs, used as a postoperative treatment for Dukes' stage C colon cancer, reduces the risk of dying within 3 years by about one third.

On the basis of laboratory experiments with colon cancer cells, investigators at the University of Leeds (England) propose that levamisole and fluorouracil have complementary effects at the level of RNA activity. Specifically, levamisole offsets 5-FU's general suppression of RNA synthesis, and both have a role in the increase and accumulation of the messenger RNAs responsible for producing a particular class of immune system proteins: Class I Human Leukocyte Antigens.

The findings suggest, the investigators say, that levamisole both reduces the toxicity that fluorouracil would otherwise exhibit because of its general suppression of RNA synthesis, and at the same time augments the therapeutic benefit of 5-FU through selective effects on certain messenger RNAs.

In an accompanying editorial, Chris H. Takimoto, MD,PhD, National Cancer Institute, notes that "this study reports the first biochemical or molecular interaction between [levamisole and 5-FU] to be demonstrated at pharmacologically relevant levamisole concentrations." He also notes, however, that the patterns of administration of the two drugs differed markedly from typical clinical drug administration schedules, which may affect the applicability of these in vitro tests to the clinical setting. Dr. Takimoto recommends validation of these results in additional laboratory research with different colon cancer cell lines and actual tumor specimens.

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