Comparison of Sulindac, Aspirin, and Ursodiol in Preventing Colorectal Cancer

OBJECTIVES: * Determine the percentage change in colorectal aberrant crypt foci (ACF) in patients with a history of colorectal cancer or at high risk for colorectal cancer when treated with sulindac vs aspirin vs ursodiol. * Determine the safety and efficacy of these drugs, in terms of ability to cause regression of existing colorectal ACF and prevent new ACF development, in these patients. OUTLINE: This is a partially blinded, randomized, placebo-controlled study. Patients are stratified according to colorectal neoplasia (adenoma vs carcinoma). Patients are randomized to 1 of 4 treatment arms. * Arm I: Patients receive oral sulindac twice daily. * Arm II: Patients receive oral aspirin once daily. * Arm III: Patients receive oral ursodiol three times daily. * Arm IV: Patients receive oral sulindac placebo twice daily. In all arms, treatment continues for 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo a colonoscopy at baseline and at the end of treatment. Patients are followed at 2 months after the end of treatment. PROJECTED ACCRUAL: A total of 172 patients (43 per treatment arm) with a history of colorectal cancer or adenomas will be accrued for this study. A total of 20 additional patients with no elevated risk of colorectal neoplasia will be accrued, but not randomized, for this study.