Preclinical studies of chemoprevention drugs given in combination at low doses show remarkable efficacy in preventing adenomas with little additional toxicities, suggesting a strategy to improve risk to benefit ratios for preventing recurrent adenomas. Three hundred seventy-five patients with history of resected (> or =3 mm) adenomas were randomly assigned to receive oral difluoromethylornithine (DFMO) 500 mg and sulindac 150 mg once daily or matched placebos for 36 months, stratified by use of low-dose aspirin (81 mg) at baseline and clinical site. Follow-up colonoscopy was done 3 years after randomization or off-study. Colorectal adenoma recurrence was compared among the groups with log-binomial regression. Comparing the outcome in patients receiving placebos to those receiving active intervention, (a) the recurrence of one or more adenomas was 41. 1% and 12 VSports手机版. 3% (risk ratio, 0. 30; 95% confidence interval, 0. 18-0. 49; P < 0. 001); (b) 8. 5% had one or more advanced adenomas, compared with 0. 7% of patients (risk ratio, 0. 085; 95% confidence interval, 0. 011-0. 65; P < 0. 001); and (c) 17 (13. 2%) patients had multiple adenomas (>1) at the final colonoscopy, compared with 1 (0. 7%; risk ratio, 0. 055; 0. 0074-0. 41; P < 0. 001). Serious adverse events (grade > or =3) occurred in 8. 2% of patients in the placebo group, compared with 11% in the active intervention group (P = 0. 35). There was no significant difference in the proportion of patients reporting hearing changes from baseline. Recurrent adenomatous polyps can be markedly reduced by a combination of low oral doses of DFMO and sulindac and with few side effects. .