A randomized trial of selenium and vitamin E for primary prevention of non-melanoma skin cancer: Trial results and experience from a low-resource setting.

1511 Background: Selenium and vitamin E supplementation previously have shown some evidence of a beneficial effect in the secondary prevention of non-melanoma skin cancer (NMSC). More than 100 million people worldwide are at increased risk of NMSC and other cancers due to arsenic exposure from drinking water and diet – a risk that persists for several decades even after the exposure has terminated. Here, we report on the design, methods and main results of the Bangladesh Vitamin E and Selenium Trial (BEST) – a population-based chemoprevention study conducted among 7,000 adults with visible arsenic toxicity. Methods: BEST is a 2 × 2 full factorial, double-blind, randomized placebo controlled trial of 7,000 adults having manifest arsenical skin lesions evaluating the efficacy of 6-year supplementation with alpha-tocopherol (100 mg daily) and L-selenomethionine (200 μg daily) for the prevention of NMSC incidence. Results: Excellent compliance was maintained through the course of the trial, based on data from pill counts, self-reported compliance, and bioadherence. Among participants on treatment through the end of the 6-year intervention period, > 85% were adherent to at least 80% of study supplements. More than 500 new NMSC cases were ascertained using a three-tiered biopsy protocol. No significant beneficial effects were observed on NMSC incidence during the study period for selenium or vitamin E. Among more than 500 observed deaths (including 182 cancer-related deaths), there were also no significant treatment effects on total mortality, cancer-related mortality or arsenical cancer-related mortality. Conclusions: This large population-based trial does not support any beneficial effect of vitamin E or selenium supplementation for the primary prevention of NMSC or mortality in an arsenic-exposed population. With the rapidly increasing burden of preventable cancers in low- and middle-income countries, efficient and feasible chemoprevention study designs and approaches, such as employed in Bangladesh, may prove impactful in conceiving large scale cancer chemoprevention trials in low-resource settings. Clinical trial information: NCT00392561.