Reducing Colorectal Cancer Risk
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By Cori Vanchieri

Reducing Colorectal Cancer Risk

Arthritis drug links to fewer potentially precancerous polyps, but also to cardiovascular problems

By Cori Vanchieri


A long-awaited answer is here: Two large studies provide the first convincing evidence that the arthritis drug Celebrex (celecoxib) reduces the number of colorectal polyps, called adenomas, in people at high risk for colorectal cancer who have already had at least one polyp removed. However, too many questions remain about the drug's side effects for researchers to confidently recommend it as a cancer preventive.

In both studies, a U.S.-based trial with 2,035 patients and an international trial with 1,561 patients, those taking Celebrex had about 33 percent to 45 percent fewer adenoma recurrences, depending on the dose they took, than did patients taking a placebo. Invasive cancers were also reduced, and people who did get colorectal cancer while on Celebrex had smaller and fewer tumors than those taking a placebo. The results of both studies were presented at the annual meeting of the American Association for Cancer Research in April.

The current challenge facing researchers is to deal with the increased risk of serious heart attack and stroke that appears to accompany the drug. The cardiovascular risk was first revealed in 2004, when several similar drugs were linked to deaths due to heart problems. Those drugs include Vioxx (rofecoxib), Bextra (valdecoxib) and Celebrex. In the new Celebrex studies, the number of cardiovascular problems was small but, of course, caused concern.

In the U.S. trial, seven patients (1 percent) in the placebo group had serious cardiovascular events, compared with 16 (2.3 percent) in a group taking 200 milligrams of Celebrex daily and 23 (3.4 percent) in a 400-milligrams-per-day group.

In the international trial, 12 patients (1.9 percent) in the placebo arm had a cardiovascular event, compared with 23 (2.5 percent) in the study's Celebrex arm, who were given 400 milligrams daily. "Celecoxib is effective, but we can't recommend it for prevention of sporadic colorectal adenomas until cardiovascular toxicity is dealt with," says surgeon Monica Bertagnolli of Harvard University, who presented the U.S. study results. Both studies were funded by Pfizer, the maker of Celebrex.

Colorectal cancer screening has been proven to reduce cancer deaths. However, because too few people get these screening tests—recommended for all men and women age 50 and older (and some younger people if they have risk factors)—scientists have been looking for additional ways to help prevent the disease. Their hopes remain high for COX-2 inhibitors like Celebrex that block the COX-2 pathway, which is overstimulated during development of certain cancers, including colorectal cancer.

Patients who went into these two studies with certain cardiovascular risk factors, such as hypertension, were at highest risk for the side effects. It may be possible, therefore, to determine which patients should take COX-2 inhibitors based on their risk profile for both colorectal cancer and cardiovascular disease.

National Cancer Institute medical oncologist Ernest Hawk, who has overseen NCI studies of COX-2 inhibitors, sums it up: "With efficacy of this magnitude [in colorectal polyp reduction], there is a strong impetus to try to search out how to tilt the risk-benefit equation in favor of benefit."

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