Celecoxib With vs. Without DFMO for Familial Adenomatous Polyposis

Combination therapy did not achieve a higher percent reduction in adenomas, but a video-based global assessment showed positive results.

Difluoromethylornithine (DFMO) has previously produced a significant reduction in polyp counts when combined with sulindac in treatment of familial adenomatous polyposis (FAP). In the current industry-funded randomized study, investigators compared the efficacy of celecoxib plus DFMO with celecoxib alone in reducing the number of polyps among 112 patients with FAP (mean age, 38 years).

The primary endpoint, the number of polyps, did not change with either treatment. The adenoma burden (number times diameter) decreased by 40% with combination therapy versus 27% with celecoxib alone (P=0.13). Blinded video assessment of the colon before and after treatment measured “global polyp change” and showed a significantly greater reduction with combination therapy versus celecoxib alone (80% vs. 33%). Hearing loss, which is a concern with DFMO, occurred but was not significantly different between the study groups.

Comment

This study was long and tedious for investigators to perform, and results had to be interpreted as negative, though the authors appropriately questioned whether they chose the wrong primary endpoint. Certainly, the blinded video-based global change result is impressive and suggests that DFMO has a real benefit that could not be demonstrated with polyp counts. Also, the overall magnitude of benefit with sulindac has been greater than celecoxib (there are no direct head-to-head comparisons of the two nonsteroidal anti-inflammatory drugs [NSAIDs]), and sulindac is generally considered the drug of choice in patients who can tolerate a nonselective NSAID. An important clinical issue is the need for effective therapeutic options in patients with innumerable small bowel polyps, and determining whether DFMO could help manage these patients is worth further study.

Reviewing Author

Douglas K. Rex, MD

Disclosures

Consultant/Advisory BoardOlympus Corporation America; Boston Scientific

Speaker’s BureauOlympus

Grant/Research SupportMedtronic; Boston Scientific; Colonary Solutions; Paion Medical; Medivators; Braintree Laboratories

Editorial BoardsWorld Journal of Gastroenterology; The Journal of Clinical Gastroenterology; Techniques in Gastrointestinal Endoscopy; Gastroenterology & Hepatology; Expert Review of Gastroenterology & Hepatology; Medscape Gastroenterology; World Journal of Gastrointestinal Pharmacology and Therapeutics; Annals of Gastroenterology & Hepatology; World Journal of Gastrointestinal Oncology; Comparative Effectiveness Research; Journal of Anesthesia & Clinical Research; Gastroenterology; World Journal of Gastrointestinal Pathophysiology; Gastroenterology Research and Practice; GI & Hepatology News; Gastroenterology Report; Clinical Epidemiology Reviews; JSM Gastroenterology and Hepatology; GI Journal Watch; Austin Journal of Gastroenterology; World Journal of Gastrointestinal Pharmacology & Therapeutics

Leadership Positions in Professional SocietiesAmerican Society for Gastrointestinal Endoscopy (Treasurer); US Multi-Society Task Force (AGA, ACG, ASGE) (Chair)