Patients who have been curatively treated for early stage cancers of the oral cavity, pharynx, and larynx have an exceptionally high risk for developing second cancers. These second cancers include new primary tumors, which occur at a rate of about 4% per year, as well as recurrent tumors. New primary tumors generally occur in the oral cavity, pharynx, larynx, esophagus, or lung, and are a consequence of field cancerization of the entire mucosal surface of the upper aerodigestive tract. Overall, treatment failure due to second primary tumors and local recurrences occurs in approximately 35% of Stage I/II patients five years of follow- up. This exceptional risk is a significant cancer control problem which potentially could be modified by appropriate interventions. Evidence from epidemiologic studies, clinical studies and animal tumor models suggests that supplemental beta-carotene may inhibit the development of second cancers in this patient population. Consequently, we propose to continue to recruit patients to a randomized, double-blind placebo-controlled trial to test the primary hypothesis that daily administration of 50 mg beta- carotene will lower the incidence of second cancers. This trial began enrolling patients in 1991, and has enrolled 168 and randomized 149 patients as of September 1993. We propose to recruit a total of 480 patients with two additional years of recruitment at two sites, and then follow the subjects for at least an additional three years. The study population consists of patients with recently diagnosed squamous cell carcinoma of the oral cavity, pharynx or larynx throughout Connecticut and South Florida. Following curative treatment, eligible patients with Stage I/II disease are invited to participate in the study. After a brief placebo run-in period, subjects are randomized to receive beta-carotene or placebo as a daily supplement. Patients are followed for disease by their regular physician with the endpoint being local recurrence or the occurrence of a second primary cancer in the oral cavity, pharynx, larynx, esophagus or lung. This project also has the following secondary aims: (a) to examine whether this patient population will take and tolerate daily supplements of beta-carotene over a period of years; (b) to assess compliance more formally in a sub-group of participants by using microelectronic monitoring, where standard pill bottles are fitted with a cap that contains a microprocessor that records each bottle opening and closing as a presumptive dose, and (c) to obtain prospective data to determine whether the risk for second primary tumors depends upon age or gender, site of the initial cancer, treatment (irradiation versus surgery) of the initial cancer, diet, and the presence or absence of continuing tobacco and alcohol exposures.
