A randomized trial comparing ursodeoxycholic acid and rofecoxib, a selective Cox-2 inhibitor, in the treatment of advanced duodenal adenomas in patients with familial adenomatous polyposis

Abstract

Background: Following prophylactic proctocolectomy, the most common cause of death in patients with familial adenomatous polyposis (FAP) is periampullary adenocarcinoma. Prophylactic duodenal resection is not generally practiced, because of the significant associated morbidity, and the relatively lower incidence of perlampullary edenocarcinoma, A drug that could induce polyp regression or inhibit polyp formation is needed for the management of FAP patients with advanced duodenal adenomas. Methods: patients with the diagnosis of FAP based on previous genotypic and phenotypic assessments, with known severe duodenal polyposis (Stage III or IV) based on previous endoscopic evaluation, were eligible. Baseline side-viewing upper endoscopy was carried out, and videotaped. Eligible patients with stage Ill or IV duodenal polyposis were then assigned to receive rofecoxib 25rag/day or ursodeoxycholic acid 13mg/kg/day, based on a computer generated randomization schedule. The treatment was for a period of six months, and was followed by repeat endoscopy. The videos of the endoscopies were then assessed by reviewers blinded to the time of the endoscopy, and to the treatment received. The videos were classified as better, worse, or the same. Results: Nineteen patients were randomized, nine received rofecoxib and 10 received ursodenxycholic acid. Three patients withdrew from the study, two from the ursodeoxycholic acid group, and one from the rofecoxib group. Preliminary results showed some improvement in two of six patients who have completed follow-up endoscopy in the rofecoxib treated grOup. None of the six patients treated with ursodeoxycholic acid have shown improvement. There was no progression of the duodenal adenomas in any of the patients. Both patients who responded had stage III disease. None of the patients with stage IV disease showed regression. Conclusions: The Cox-2 inhibitor may be more effective in causing duodenal polyp regression. None of the patients with more advanced (stage IV) duodenal disease had polyp regression, suggesting that efforts to cause polyp regression might be more successful when directed at earlier, less advanced adenomas. A large, multicenter trial is needed to determine the role of cox-2 inhibitors in these patients