HOUSTON - An international team of scientists reports that a single 400-milligram daily dose of celecoxib, commonly called Celebrex® and manufactured by Pfizer, significantly reduced recurrence of adenomas, or pre-malignant colon tumors - within three years of previous adenoma removal.
The New England Journal of Medicine today published findings from the Prevention of Spontaneous Adenomatous Polyps (PreSAP) study, involving more than 1,550 participants at 107 sites in 32 countries on six continents. The study was led by Nadir Arber, M.D., chair of the Integrated Cancer Prevention Center and professor of medicine and gastroenterology at the Tel Aviv Sourasky Medical Center and Bernard Levin, M.D., 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.
As excess amounts of the protein cyclooxygenase (COX-2) are associated with adenomas and colon cancer, PreSAP researchers studied celecoxib - a selective COX-2 inhibitor - to prevent 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.
In the placebo-controlled, double-blind PreSAP trial, study leaders randomly assigned participants to receive either a single 400-mg dose of 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 burdens for participants. All polyps were removed and examined by study pathologists.
At the conclusion of the trial, the cumulative adenoma rate for the celecoxib study group was 33.6 percent, while the cumulative rate of adenoma development in 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 Celebrex®, Aleve® and Motrin®, 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, APC 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."
Levin has served as a consultant for Pfizer, which provided grant support for the PreSAP trial. These arrangements are managed by M. D. Anderson in accordance with its conflict of interest policies.
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