Abstract A80: Antioxidant supplement and long-term reduction of metachronous adenomas of the large bowel: Results of a double-blind randomized trial

Abstract

Abstract This is a double randomized trial aimed at evaluating the efficacy of antioxidants in reducing the incidence of metachronous adenomas (MA) of the large bowel after endoscopic polypectomy. A 50% reduction in the incidence of MA was expected in patients (pts) allocated to an active compound (intervention) arm as compared to those assigned to a placebo. Eligible for the study were pts aged 25–75 years with a clean colon after adenomas removal. Pts with FAP, invasive carcinoma in adenoma, previous polypectomy, IBD, bowel resection, cancer at any site, life-threatening diseases, current use of vitamins or calcium were excluded. Pts were randomly allocated to receive daily, for 5 years, either an antioxidant compound (selenomethionine 200 g, zinc 30 mg, vitamin A 6000 IU, vitamin C 180 mg and vitamin E 30 mg) or a placebo, both were provided by Pharma Nord. Total Colonoscopy (TC) was planned on year one, three and five after randomization and then according to current guidelines. The primary endpoint of the study was the occurrence of MA detected during TC examinations. The study was approved by the Ethical Committee of the Natl. Institute for Cancer Research of Genoa. Three GI endoscopy units in northern Italy participated in the study. The study started on March 1988 and was stopped on June 1996 when 411 patients had been enrolled. Of them, 200 were assigned to the intervention arm and 211 to the placebo arm. On June 2009, information on survival was available for 396 pts (96.4%); follow up information (at least one TC performed after randomization) was available for 311 pts (80.5%): 165 in the intervention and 166 in the placebo arm. Predictors of MA (gender, age, number of adenomas and rate of advanced adenomas) were similar in pts who had follow up TC and in those who were lost. Of the 311 patients, 144 (43.5%) assumed more than 2/3 of the total amount of the assigned treatment: the rates were similar in the two arms. An intention to treat analysis was performed. The 311 pts provided 1.743 py of follow-up and 98 pts developed MA (2 with invasive carcinoma). The observed incidence of MA was 4.2% (37 cases/886 py) in the intervention arm and 7.2% (62 cases/857 py) in the placebo arm (crude RR=0.56, 95% CI 0.36–0.87; P=0.007). The 15-year actuarial MA-free survival was 48.3% in pts assigned to the intervention arm and 30.5% in those assigned to the placebo arm (P=0.006). A Cox proportional hazard model was fitted to the data and GI endoscopy unit, gender, age, number of adenomas, presence of advanced adenoma were included in the model as covariates: a 41% reduction in the risk of MA was observed in the intervention as compared to the placebo arm (HR=0.59, 95% CI 0.39–0.90; P=0.013). Among pts who had advanced adenomas at randomization, those assigned to the intervention arm had a 10-fold lower risk of advanced MA as compared to those assigned to the placebo (RR=0.11, 95%CI 0.02–0.49; P=0.004). To our knowledge, this is the first time that a specifically designed trial shows the persistence of a statistically significant reduction of colorectal MA in pts treated with a selenium-based antioxidant compound long time after the treatment cessation. In particular, the effect observed in pts with advanced index adenoma is intriguing. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A80.