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Celecoxib for Prevention of Colorectal Polyps

Although risk for recurrent adenomas was lowered, this benefit might be outweighed by adverse cardiovascular effects.

Because cyclooxygenase 2 (COX-2) is overexpressed in colorectal adenomatous polyps, selective inhibition of COX-2 potentially could prevent them. Two trials designed to test this theory — APPROVe with rofecoxib (Vioxx) and APC with celecoxib (Celebrex) — were halted in 2004, because COX-2 therapy was associated with increases in adverse cardiovascular events. Rofecoxib was removed from the market, but celecoxib still is available, and its effect on polyp prevention remains of interest. We now have the results of two large industry-sponsored randomized trials of celecoxib for prevention of adenomatous polyps; the trials included patients with recently removed colorectal adenomas, but excluded patients with familial polyposis.

In PreSAP, more than 1500 patients received once-daily celecoxib (400 mg) or placebo. At 3 years, celecoxib recipients were significantly less likely than placebo recipients to have developed any colorectal adenoma (34% vs. 49%) or an adenoma defined as advanced because of large size or histologic features (5% vs. 10%). Serious cardiovascular events occurred in 2.5% and 1.9% of the celecoxib and placebo groups, respectively (a nonsignificant difference).

In APC, more than 2000 patients received celecoxib at one of two doses (400 or 200 mg twice daily) or twice-daily placebo. At 3 years, the proportions of patients who had developed any colorectal adenoma were 38%, 43%, and 61% with higher-dose celecoxib, lower-dose celecoxib, and placebo, respectively; advanced adenomas also developed less often in the celecoxib groups than in the placebo group (6% and 8% vs. 17%). Serious adverse cardiovascular events occurred significantly more often with celecoxib than with placebo (3.4% and 2.6% vs. 1%).

Comment: These trials show that celecoxib reduces risk for colorectal adenomas among patients with previous adenomas. Although long-term treatment presumably would result in lower long-term risk for colorectal cancer, that premise has not yet been proven. According to an analysis by editorialists, the cardiovascular toxicity of celecoxib probably would outweigh the cancer prevention benefits. They conclude, therefore, that "celecoxib has no role as a chemopreventive agent . . . in patients with nonfamilial colonic adenomas."

— Allan S. Brett, MD

Published in Journal Watch General Medicine August 30, 2006

Citation(s):

Arber N et al. Celecoxib for the prevention of colorectal adenomatous polyps. N Engl J Med 2006 Aug 31; 355:885-95.

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• Medline abstract (Free)

Bertagnolli MM et al. Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med 2006 Aug 31; 355:873-84.

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Psaty BM and Potter JD. Risks and benefits of celecoxib to prevent recurrent adenomas. N Engl J Med 2006 Aug 31; 355:950-2.

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• Medline abstract (Free)