According to two articles recently published in the New England Journal of Medicine, the cyclooxygenases 2 (COX-2) inhibitor Celebrex® (celecoxib) reduces the risk of pre-cancerous colorectal tumors (adenomas) among patients with previously diagnosed colorectal adenomas. However, the use of Celebrex is associated with an increased risk in cardiovascular side effects.
Colorectal cancer is the second leading cause of cancer-related deaths in the U.S. The disease develops in the colon (the longest part of the large intestine) or the rectum (the last several inches of the large intestine). It also may start as a precancerous growth known as an adenomatous polyp or adenoma. It is thought that a reduction in the development of adenomas would ultimately reduce the risk of developing colorectal cancer.
Celebrex belongs to the class of drugs known as non-steroidal anti-inflammatory agents. Celebrex inhibits the COX-2 enzyme, which plays a role in inflammatation.
The COX-2 enzyme is overexpressed in many colorectal cancers, suggesting that inhibiting this enzyme may contribute to prevention or treatment of the disease. Some studies, however, have linked COX-2 inhibitors with an increased risk of cardiovascular problems.
Results from two clinical trials of Celebrex were recently published in the New England Journal of Medicine. Both trials evaluated whether Celebrex stops the growth precancerous colorectal polyps.
The trials enrolled patients who had already had colorectal polyps removed. Patients were then assigned to treatment with Celebrex or placebo (inactive substitute) and were monitored for development of new colorectal polyps. Both studies assessed long-term use of higher doses of Celebrex.
The first clinical trial was referred to as the Prevention of Colorectal Sporadic Adenomatous Polyps trial and included 1,561 patients who had prior adenomas removed. Of these patients, 840 were treated with celecoxib, and 557 patients received placebo. Follow-up colonoscopies were performed to identify adenomas or colorectal cancers.
- During three years colorectal adenomas were detected in 33.6% of patients treated with Celebrex, compared with 49.3% of patients who received placebo.
- During three years advanced adenomas were detected in 5.3% of patients treated with Celebrex, compared with 10.4% of patients who received placebo.
- Serious side effects affecting the heart (cardiovascular) occurred in 2.5% of patients treated with Celebrex, compared with 1.9% of those who received placebo.
The second clinical trial was conducted to evaluate different dosages of Celebrex compared to placebo in patients with previous colorectal adenomas. This trial included 679 patients who received placebo, 685 patients who were treated with low-doses of celecoxib, and 671 patients who were treated with higher doses of celecoxib.
- Within three years, follow-up colonoscopies identified adenomas in nearly 61% of patients who received placebo; 43.2% of patients treated with lower doses of Celebrex; and 37.5% of patients treated with higher doses of Celebrex.
- The risk of cardiovascular side effects was significantly increased with the use of Celebrex, particularly at higher doses.
The researchers concluded that the use of Celebrex significantly reduces the risk of subsequent colorectal adenomas in patients with previously diagnosed adenomas. However, the use of Celebrex is also associated with an increased risk of cardiovascular side effects and therefore may not be safe for all patients.
Patients with a history of colorectal adenomas may wish to speak with their physician regarding their individual risks and benefits of the use of Celebrex.