RETINOIDS AND CHEMOPREVENTION - CLINICAL AND BASIC STUDIES

Retinoids, which include natural vitamin a (retinol) and its esters an d synthetic analogues, are the best-studied class of agents in chemopr evention. There are more than 4,000 different retinoids which have a w ide spectrum of preclinical activities, structures, pharmacological pr ofiles, tissue distributions, receptor specificities, and toxicities. A number of retinoids have significant activity in many in vivo experi mental systems including skin, bladder, lung, breast and oral carcinog enesis. In clinical trials, several retinoids have achieved significan t activity in the reversal of head and neck, skin,and cervical premali gnancy, and in the prevention of second primary tumors associated with head and neck, skin, and non-small cell lung cancer. Since 1984, our group has conducted a series of clinical trials to explore the chemopr eventive potential of 13-cis-retinoic acid (13cRA) in the aerodigestiv e tract. We have conducted two consecutive randomized studies in subje cts with premalignant lesions of the oral cavity. These studies showed that high-dose 13cRA alone can achieve significant short-term reversa l of oral premalignancy, and that high-dose followed by low-dose 13cRA can maintain suppression of oral carcinogenesis. Three other randomiz ed trials have confirmed significant retinoid activity in this human c arcinogenic system. We also developed a randomized, placebo-controlled trial of adjuvant high-dose 13cRA in patients with head and neck canc er. Second primary tumor development was significantly decreased in th e 13cRA group, but 13cRA had no impact on primary disease recurrence o r survival. This presentation will update the current status of clinic al trials and correlative laboratory studies of potential intermediate endpoint biomarkers in retinoid chemoprevention of aerodigestive trac t carcinogenesis. (C) 1995 Wiley-Liss, Inc.