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ONCOLOGY

Use of NSAIDs for the Chemoprevention of Colorectal Cancer

Drug Development Fellow, University of North Carolina School of Pharmacy, Chapel Hill, NC; Glaxo-SmithKline, Research Triangle Park, NC
Associate Professor and Vice Chair, Division of Pharmacotherapy, School of Pharmacy, University of North Carolina, Chapel Hill, NC

Reprints: Celeste Lindley PharmD FCCP FASHP BCOP, Division of Pharmacotherapy, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27577-7360, FAX 919/962-0644, celeste_lindley{at}unc.edu

OBJECTIVE: To discuss the role of nonsteroidal antiinflammatory drugs (NSAIDs) in the chemoprevention of colorectal cancer.

DATA SOURCES: A MEDLINE search (1966–May 2003) was performed to identify key literature. Search items included, but were not limited to, NSAIDs, colorectal cancer, chemoprevention, cyclooxygenase-2 (COX-2)–specific inhibitors, and familial adenomatous polyposis (FAP).

STUDY SELECTION AND DATA EXTRACTION: The search included experimental (in vitro and animal models) and clinical studies evaluating the use of NSAIDs for the chemoprevention of colorectal cancer. The MEDLINE search was supplemented by references from selected articles.

DATA SYNTHESIS: Numerous experimental, epidemiologic, and clinical studies suggest that NSAIDs have promise as anticancer agents. The mechanism by which NSAIDs lead to decreased colon carcinogenesis is not fully understood, but may involve restoration of apoptosis and inhibition of prostaglandin-mediated angiogenesis. Compelling evidence from many observational studies has consistently documented a 40–50% reduction in the risk of adenomatous polyps, colorectal cancer incidence, and mortality in patients using NSAIDs. Recent randomized, controlled trials have demonstrated a benefit with aspirin in reducing the rate of development of new or recurrent adenomas in high-risk patients. In addition, randomized studies using sulindac and celecoxib in patients with FAP have documented significant regression of existing adenomatous polyps.

CONCLUSIONS: Inhibition of COX-2 is an example of a targeted approach to the chemoprevention of colorectal cancer. However, controversy exists about the safety, efficacy, and optimal treatment regimen of NSAIDs as long-term chemopreventive agents in the general population. Ongoing studies in high-risk patients with both selective and nonselective COX inhibitors will provide important information in the area of colorectal chemoprevention, but clinical trials' use of adenomas as surrogate markers for chemoprevention trials makes their application to the general population limited.

Key Words: aspirin, colorectal cancer, COX-2, NSAIDs

Published Online, October 3, 2003. www.theannals.com, DOI 10.1345/aph.1C489

THIS ARTICLE IS APPROVED FOR CONTINUING EDUCATION CREDIT
ACPE UNIVERSAL PROGRAM NUMBER: 407-000-03-036-H01