Chemoprevention of oral cancer: beta-carotene and vitamin E in leukoplakia.

The most definitive and direct way to show that a putative chemoprevention agent actually prevents cancer would be to demonstrate a reduction in cancer incidence in a clinical trial. From a practical standpoint this approach is not feasible for most cancers. Therefore, it becomes necessary to draw conclusions on chemopreventive activity through consideration of indirect lines of evidence, one of which is activity in premalignant lesions such as leukoplakia. As a corollary, it must be emphasized that the goal of undertaking chemoprevention trials in oral leukoplakia is to develop approaches for the prevention of oral cancer. Because the risk of cancer in the usual leukoplakia lesion is low, only non-toxic agents should be tested in this setting and they should be suited for eventual use in a prevention setting. Beta-carotene and vitamin E, unlike the retinoids, fulfill the criteria for a suitable chemopreventive agent and several lines of evidence point to a preventive role for them against oral cancer. These include laboratory in vitro and animal model findings, but the strongest evidence comes from epidemiologic studies which uniformly suggest protection by beta-carotene against head and neck cancer. Much like the retinoids, but without toxicity, beta-carotene and vitamin E can produce regression of oral leukoplakia, a premalignant lesion for oral cancer, as has now been shown in eight clinical trials, five with beta-carotene alone, one with vitamin E alone and two that used these agents as part of combinations.(ABSTRACT TRUNCATED AT 250 WORDS)