Heart Risks Offset Polyp Prevention Benefit for Celebrex

August 30, 2006

BOSTON -- Celebrex (celecoxib) can prevent sporadic colorectal adenomas, as well as reduce post-polypectomy recurrences, but these pluses may be outweighed by cardiovascular minuses.

BOSTON, Aug. 30 -- Celebrex (celecoxib) can prevent sporadic colorectal adenomas, as well as reduce post-polypectomy recurrences, but these pluses may by outweighed by cardiovascular minuses.

Moreover, neither of the two trials reported in the Aug. 31 issue of the New England Journal of Medicine trial was powered to determine a role for Celebrex in the prevention of colon cancer.

Nonetheless, reductions in polyps observed in both the APC study (Adenoma Prevention with Celecoxib) and the PreSAP (Prevention of Colorectal Sporadic Adenomatous Polyps) were significant.

Surgical oncologist Monica M. Bertagnolli, M.D., of Brigham and Women's Hospital here and her ACP co-investigators reported that three years of treatment with 200 mg of Celebrex twice daily reduced the rate of detectable polyps by 33% and 400 mg twice daily reduced rate by 45%, compared with placebo (P

Both trials were suspended on Dec. 17, 2004, on the basis of the increased risk of cardiovascular events in the Celebrex arms.

Although the studies confirmed that Cox-2 inhibitors reduce the rate of recurrent adenomatous polyps, "the thought of taking a medicine every day to prevent a little benign tumor, when that medicine could cause serious side-effects just doesn't make sense," commented Steven H. Itzkowitz, M.D. a professor of gastroenterology and associate professor of oncological sciences at the Mount Sinai School of Medicine in New York.

Dr. Itzkowitz was not involved in either the ACP or PreSAP trials but was an investigator on the Vioxx (rofecoxib) study that showed that it reduced familial adenomatous polyposis. "But it (Vioxx) didn't prevent colon cancer."

By contrast, he said, colonoscopy "is extremely effective and can prevent cancers by as much as 75% to 90% in people who have had a polyp removed."

This same theme was echoed in an editorial by Bruce M. Psaty, M.D., Ph.D., and John D. Potter, M.B., B.S., Ph.D. of the University of Washington in Seattle, who wrote that even though Celebrex did a slightly better job of preventing advanced adenomas than aspirin has done in prevention trials, cardiovascular events are almost five times as common as colorectal cancer.

"Because aspirin decreases the risk of coronary disease (4.4 fewer events in 1,000 people followed over three years), and because [Celebrex] increases the risk of coronary disease (12.7 extra events), the use of [Celebrex] in 1,000 patients for three years, under the assumptions of simple risk-benefit analysis, result in 16.7 times more colorectal-cancer and cardiovascular events than treatment with low-dose aspirin and in 11.1 more events than no treatment at all," they wrote.

Drs. Psaty and Potter said that it is now "reasonable to conclude that [Celebrex] has no role as a chemopreventive agent either in patients with nonfamilial colonic adenomas or in the general population."

The ACP study was supported by the National Cancer Institute and Pfizer, while the PreSAP trial was supported by Pfizer, which markets Celebrex. In both trials investigators reported receiving financial support from Pfizer. Dr. Arber also reported that he owned Pfizer stock.