Frank L. Meyskens, Jr, MD

The article by Kelloff et al is a useful, comprehensive review of the current strategy underlying the development of clinically useful chemoprevention agents. One important topic that is not addressed in the article is the failure of micronutrients (selected on the basis of favorable epidemiologic finding) when tested as chemopreventive agents in clinical trials. Two examples of this are particularly noteworthy: In two large randomized trials involving heavy current or former smokers, b-carotene supplementation resulted in an increase in lung cancers compared to placebo.[1,2] Also, in two large randomized trials, folic acid supplementation had no effect on the natural history of cervical intraepithelial neoplasia.[3,4]