Head and Neck Chemoprevention: Recent Advances

BACKGROUND: Head and neck cancers are important to human life and health in both developed and underdeveloped countries. Management of established cancers is difficult, and there is great interest in evaluating methods to prevent these tumors from developing. METHODS: The biology of carcinogenesis, including field carcinogenesis, is reviewed, together with the biology and pharmacology of the retinoids. Intervention studies of premalignant lesions have led to prospective clinical trials of the capability of various retinoids to reduce the incidence of new second cancers. RESULTS: High-dose 13-cis-retinoic acid (13cRA) has significant activity in reversing oral leukoplakia but at a cost of substantial toxicity, and relapses occur early. An ongoing intergroup trial is underway to evaluate the capacity of low-dose (30 mg/d) 13cRA given for three years to reduce the incidence of second primary tumors in patients with "cured" squamous head and neck cancers. CONCLUSIONS: Molecular studies of loss of heterozygosity and p53 gene mutations are advancing our understanding of field carcinogenesis and the biology, pharmacology, and effects of the retinoids used in cancer prevention. Translation of early clinical trials into large-scale intervention trials to prevent second cancers are now underway.