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.
The differences between the placebo and celecoxib groups was substantial.
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."
Drugs have trade-offs. As better methods of detecting risks are developed we'll gain better ways to estimate the risks each of us face. We do not all share the same levels of risk of cancer, stroke, heart disease, and other killers. A person at great risk of colon cancer but low risk of heart disease and stroke would gain far more from celecoxib than someone with the opposite pattern of relative risks.
A couple of other recent papers give a sense of the interest medical researchers have in celecoxib against cancer: Celecoxib and Curcumin Synergistically Inhibit the Growth of Colorectal Cancer Cells and Radiosensitivity Enhancement by Combined Treatment of Celecoxib and Gefitinib on Human Lung Cancer Cells. Celecoxib might also slow the development of prostate cancer. Celecoxib might also be helpful against breast cancer.
Generally, COX-2 works by regulating the production of prostaglandins in cells. In the Mayo study, celecoxib reduced levels of COX-2 protein in mammary tumor cells; the therapy was even more effective in minimizing the amounts of COX-2 dependent prostaglandin E metabolites in mammary tumor cells.
“Celecoxib treatment appears to exert its antiproliferative, antiangiogenic, and pro-apoptotic effects by regulating the prostaglandin pathways,” Mukherjee said. “This leads to the reduction in primary breast tumor mass.”
She noted that in an experiment with a limited number of mice, celecoxib appeared to completely inhibit metastasis of the breast tumor.
A COX-2 inhibitor is not going to cure cancer all by itself. But all the ways that cancer cells differ from regular cells make potential targets for drugs that target those differences. Some cancers will get cured by using multiple drugs to target many differences of cancer cells at once. Celecoxib should be seen as a potential player in multi-drug therapies aimed at hitting cancer cells in many ways at once.
|Share |||Randall Parker, 2006 August 31 09:43 PM Biotech Cancer|