Effect of COX and EGFR Inhibition on Duodenal Neoplasia in Familial Adenomatous Polyposis: A Randomized Placebo-Controlled Trial

Familial adenomatous polyposis (FAP) is caused by mutations in the APC gene and is characterized by the development of hundreds of colorectal adenomas and eventually colorectal cancer. FAP patients are also at increased risk for duodenal neoplasia, with duodenal adenomas forming in >50% and up to a 15% lifetime risk of duodenal carcinoma. Multiple studies have shown that sulindac inhibits colorectal adenomas in FAP patients, however, they have failed to show significant reduction in duodenal adenomas. Preclinical data has shown that the combination of COX and EGFR inhibition diminished small intestinal adenoma development by 87% in mice with germline Apc mutations.