Randomized trial of supplemental beta-carotene to prevent second head and neck cancer

beta -carotene has established efficacy in animal models of oral carcinogen esis and has been shown to regress oral precancerous lesions in humans, The purpose of this study was to see whether these effects extended to the pre vention of oral/pharyngeal/laryngeal (head and neck) cancer in humans. The subject population for this randomized, placebo-controlled, double-blinded clinical trial included 264 patients who had been curatively treated for a recent early-stage squamous cell carcinoma of the oral cavity, pharynx, or larynx, Patients were assigned randomly to receive 50 mg of beta -carotene per day or placebo and were followed for up to 90 months for the developmen t of second primary tumors and local recurrences, After a median follow-up of 51 months, there was no difference between the two groups in the time to failure [second primary tumors plus local recurrences: relative risk (RR), 0.90; 95% confidence interval (CI), 0.56-1.45]. In site-specific analyses, supplemental beta -carotene had no significant effect on second head and n eck cancer (RR, 0.69; 95% CI, 0.39-1.25) or lung cancer (RR, 1.44; 95% CI, 0.62-3.39). Total mortality was not significantly affected by this interven tion (RR, 0.86; 95% CI, 0.52-1.42), Whereas none of the effects were statis tically significant, the point estimates suggested a possible decrease in s econd head and neck cancer risk but a possible increase in lung cancer risk , These effects are consistent with the effects observed in trials using in termediate end point biological markers in humans, in which p-carotene has established efficacy in oral precancerous lesions but has no effect or slig htly worsens sputum cytology, and in animal carcinogenicity studies, in whi ch p-carotene has established efficacy in buccal pouch carcinogenesis in ha msters but not in animal models of respiratory tract/lung carcinogenesis, w ith some suggestions of tumor-promoting effects in respiratory tract/lung, If our results are replicated by other ongoing/completed trials, this sugge sts a critical need for mechanistic studies addressing differential respons es in one epithelial site (head and neck) versus another (lung).