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May 15, 1996

Carcinogenicity of Lipid-Lowering Drugs-Reply

Author Affiliations

University of California, San Francisco

JAMA. 1996;275(19):1481-1482. doi:10.1001/jama.1996.03530430023031

In Reply.  —Dr Cattley emphasizes the sensitivity of rodents to peroxisomal proliferation as the cause of their susceptibility to fibrate-induced liver cancer. This is only partly reassuring because mild peroxisomal proliferation does occur in humans and because the fibrates also cause Leydig cell tumors in rats. More important, clinical trials1 suggest that fibrates may increase mortality in humans so rodent carcinogenicity has less marginal weight in clinical decisions involving fibrates than is the case for the statins. Peroxisomal proliferation is not a factor for the statins.We agree with Dr Illingsworth that the exposure of the liver to drugs taken orally exceeds that indicated by peripheral blood measurements. However, the FDA preference for basing equivalency on blood levels is appropriate for lung, thyroid, and testis tumors (each observed with at least 2 cholesterol-lowering drugs), and for malignant lymphomas (observed with pravastatin).We appreciate Dr Laws' letter and regret that