Chemoprevention

The discovery of cyclooxygenase enzyme (COX1, COX2) overexpression in colorectal polyps and cancer has led to numerous studies evaluating nonsteroidal anti-inflammatory drugs (NSAiDs) in the treatment of FAP. Numerous studies involving Sulindac have shown a decrease in size and number of colorectal polyps (65% and 56%, respectively) in patients with FAP after several months of therapy.[24] Nevertheless, growth resumes as soon as therapy is stopped and there have been no studies to determine the safety of long-term Sulindac therapy. There have also been reported cases of colorectal cancer occurring while on Sulindac therapy. Studies are now underway to determine whether Sulindac sulfone, a metabolite of Sulindac without significant COX inhibition, will provide chemoprevention without significant side effects. In 1999, the Food and Drug Administration granted accelerated approval of Celecoxib for treatment of colorectal polyposis in FAP based on a 6-month trial that showed reduction in the number of polyps by 28% and the sum of poly diameter by 30.7% from baseline.[25] While these studies are encouraging there remain no long-term prospective studies showing improved prognosis with NSAiD therapy. Furthermore, there have been no studies that suggest that periampulary and duodenal disease responds to either of these two medications.[24]

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