Celecoxib: new indication. Colorectal cancer: no preventive benefit

(1) Familial adenomatous polyposis is a genetic disorder associated with multiple adenomatous colorectal polyps that invariably progress to colorectal cancer. Gastroduodenal polyposis and extra-gastrointestinal desmoid tumours are other major sources of morbidity in these patients. (2) The current strategy used to prevent colorectal cancer in patients with APC gene mutations consists of yearly monitoring starting in adolescence, and prophylactic colectomy in early adulthood if polyposis occurs. (3) On the basis of pathophysiological, experimental and epidemiological evidence, some specialists have postulated that certain nonsteroidal antiinflammatory drugs (NSAIDs) might have a preventive effect on colorectal adenomas and cancer. (4) Aspirin and sulindac were tested for the prevention of polyps in patients with familial adenomatous polyposis, with uncertain results and weak evidence of effectiveness. (5) Celecoxib was tested in a comparative randomised double-blind trial lasting 6 months. It involved 77 patients with familial polyposis and colorectal polyps, and 6 patients with only duodenal polyps. On the basis of composite endoscopic criteria, a celecoxib dose of 800 mg/day (but not 200 mg/day) reduced the number and surface area of adenomatous colorectal polyps in patients with familial adenomatous polyposis. It is not known whether celecoxib also reduced the risk of colorectal cancer. A global qualitative analysis suggested that celecoxib was also effective in reducing duodenal polyps. (6) Nearly one-third of patients receiving celecoxib 800 mg/day in this trial developed rectal bleeding. Another preventive trial was stopped when an excess of cardiovascular events was found in patients taking celecoxib. (7) The long-term risk-benefit balance of celecoxib 800 mg/day is not known nor whether efficacy persists after treatment discontinuation. (8) In practice, it is better not to use celecoxib to prevent colorectal cancer: its efficacy has not been demonstrated, even in familial polyposis, and it carries a major risk of bleeding and cardiovascular events.