The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis

Background: Patients with familial adenomatous polyposis have a nearly 100 percent risk of colorectal cancer. In this disease, the chemopreventive eff ects of nonsteroidal antiinflammatory drugs may be related to their inhibit ion of cyclooxygenase-2. Methods: We studied the effect of celecoxib, a selective cyclooxygenase-2 i nhibitor, on colorectal polyps in patients with familial adenomatous polypo sis. In a double-blind, placebo-controlled study, we randomly assigned 77 p atients to treatment with celecoxib (100 or 400 mg twice daily) or placebo for six months. Patients underwent endoscopy at the beginning and end of th e study. We determined the number and size of polyps from photographs and v ideotapes; the response to treatment was expressed as the mean percent chan ge from base line. Results: At base line, the mean (+/-SD) number of polyps in focal areas whe re polyps were counted was 15.5+/-13.4 in the 15 patients assigned to place bo, 11.5+/-8.5 in the 32 patients assigned to 100 mg of celecoxib twice a d ay, and 12.3+/-8.2 in the 30 patients assigned to 400 mg of celecoxib twice a day (P=0.66 for the comparison among groups). After six months, the pati ents receiving 400 mg of celecoxib twice a day had a 28.0 percent reduction in the mean number of colorectal polyps (P = 0.003 for the comparison with placebo) and a 30.7 percent reduction in the polyp burden (the sum of poly p diameters) (P = 0.001), as compared with reductions of 4.5 and 4.9 percen t, respectively, in the placebo group. The improvement in the extent of col orectal polyposis in the group receiving 400 mg twice a day was confirmed b y a panel of endoscopists who reviewed the videotapes. The reductions in th e group receiving 100 mg of celecoxib twice a day were 11.9 percent (P = 0. 33 for the comparison with placebo) and 14.6 percent (P = 0.09), respective ly. The incidence of adverse events was similar among the groups. Conclusions: In patients with familial adenomatous polyposis, six months of twice-daily treatment with 400 mg of celecoxib, a cyclooxygenase-2 inhibit or, leads to a significant reduction in the number of colorectal polyps. (N Engl J Med 2000;342:1946-52.) (C)2000, Massachusetts Medical Society.