Magazine article Drug Topics

Sorting out Relevant Data on Rodent Carcinogenicity

Magazine article Drug Topics

Sorting out Relevant Data on Rodent Carcinogenicity

Article excerpt

In the past month, questions about carcinogenicity data obtained from rodents have raised concerns that both methylphenidate (Ritalin, CibaGeneva) and some lipid-lowering agents may cause cancer in humans.

A recent study published in the Journal of the American Medical Association drew attention to the fact that certain lipid-lowering agents, the fibrates and the statins, cause cancer in rodents. This finding prompted the authors to recommend that these agents be avoided, except in patients at high short-term risk of coronary heart disease.

The article triggered a storm of controversy. Spokesmen from several pharmaceutical companies, the American Heart Association, and the National Cholesterol & Education Program stepped into the fray to refute the significance of the findings. Scott Grundy, M.D., Ph.D., chairman of the AHA's task force on risk reduction, emphasized that there is no evidence from human studies that cholesterol-lowering drugs cause cancer. In his view, there is strong justification for using these drugs in patients at high risk for coronary heart disease.

Questions about the applicability of rodent data to humans came up again a few weeks later, when CibaGeneva Pharmaceuticals and generic manufacturers changed their labeling for methylphenidate to reflect the results of toxicology studies conducted in mice. These studies showed an increase in some types of liver tumors at doses beyond the maximum recommended human dose. The Food & Drug Administration then issued a "Talk Paper" saying that the agency considers the findings a "signal of a weak cancer-causing potential for the drug" and indicated that it continues to regard methylphenidate as a safe and effective drug.

To clarify the confusion surrounding the relevance of rodent carcinogenicity data to humans, Drug Topics contacted Joseph DeGeorge, Ph.D., chairman of the carcinogenicity assessment committee at the FDA.

DeGeorge explained that all of the known human carcinogens are also carcinogenic in rodents, but, he noted, the converse isn't necessarily true; if a drug is shown to be carcinogenic in rodents, there are many reasons why the finding might not be applicable to humans. He illustrated his point by explaining that rodents metabolize some drugs differently from the way humans do. …

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