One 400-milligram daily dose of celecoxib significantly reduces risk for recurrent colon adenomas for three years after removal of existing adenomas, according to an article in the August 31 issue of the New England Journal of Medicine.

The Prevention of Spontaneous Adenomatous Polyps (PreSAP) study involved more than 1,550 participants at 107 sites in 32 countries on 6 continents. The study was led by Nadir Arber, MD, chair of the Integrated Cancer Prevention Center and professor of medicine and gastroenterology at the Tel Aviv Sourasky Medical Center and Bernard Levin, MD, vice president of Cancer Prevention and Population Sciences at The University of Texas M. D. Anderson Cancer Center.

"Celecoxib 400 mg once daily significantly reduced colorectal adenoma occurrence, with a greater effect on advanced adenomas," said Arber.

Because excess amounts of cyclooxygenase (COX-2) are associated with adenomas and colon cancer, the researchers studied the selective COX-2 inhibitor to see whether it prevented recurrence of the pre-cancerous lesions.

"There is no doubt that celecoxib is an effective agent in reducing the size and occurrence of adenomas in patients with higher risks for colorectal cancer," said Levin.

Participants were randomized to a single 400-mg dose celecoxib (approximately 930 subjects) or a placebo (nearly 630 subjects). Subjects received colonoscopies after one and three years to detect potential pre-malignant tumors and their sizes, as well the overall adenoma burden. All polyps were removed and examined by study pathologists.

At the conclusion of the trial, the cumulative adenoma rate for the celecoxib group was 33.6 percent, while the cumulative rate for the placebo group was 49.3 percent (a 36 percent reduction). Celecoxib administration was associated with a 50 percent reduction in larger, potentially more dangerous adenomas.

"Unlike the recent Adenoma Prevention with Celecoxib (APC) trial, we did not find a statistically significant increase in cardiovascular risk associated with the use of 400 mg of celecoxib once daily," said Levin. "That said, because of the significant cardiac side effects seen in the APC study, further cardiovascular research on the use of all anti-inflammatory drugs, such as CelebrexR, AleveR and MotrinR, as chemoprevention tools is warranted.

"Low dose aspirin also has been shown to reduce adenoma formation in individuals with a prior history of polyps and has the potential to decrease cardiovascular disease risk," said Levin. "However, its use is associated with an increased risk of upper-gastrointestinal bleeding and stroke."

The three-year APC study, with more than 2,000 participants, sought to reduce adenoma size and occurrence through the use of celecoxib. In the study, researchers administered celecoxib twice daily at either 200 mg or 400 mg doses. The study showed that the drug nearly doubled cardiovascular risk to participants.

"While our findings are exciting in that they suggest great potential for reducing adenoma formation in patients with high risk for colorectal cancer, we've scratched the surface with the PreSAP trial," said Levin. "Until these impressive prevention results are realized with lessened cardiovascular risk, we cannot advise celecoxib routinely as a tool for colon cancer prevention. Once daily dosing may provide an important insight into ways to diminish the untoward cardiovascular effects of celecoxib."