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Development of COX Inhibitors in Cancer Prevention and Therapy

Umar, Asad, Ph.D., D.V.M.; Viner, Jaye L., M.D., M.A.; Anderson, William F., M.D., M.P.H.; Hawk, Ernest T., M.D., M.P.H.

American Journal of Clinical Oncology: August 2003 - Volume 26 - Issue 4 - p S48-S57
doi: 10.1097/01.COC.0000074157.28792.02

On the strength of in vitro, in vivo, observational, and clinical data, nonsteroidal antiinflammatory drugs (NSAIDs)—also referred to as COX inhibitors—have emerged as lead compounds for cancer prevention, and possible adjuncts to cancer therapy. Thus far, the routine use of NSAIDs for these indications is limited, largely owing to toxicity concerns, the paucity of efficacy data for any specific target organ, and uncertainties with regard to the most appropriate regimen (i.e., the best agent, formulation, dose, route of administration, and duration). Strategies to address these concerns primarily aim to improve the therapeutic index (i.e., benefit:risk ratio) of COX inhibitors by 1) minimizing systemic exposures whenever feasible, 2) achieving greater mechanistic specificity, 3) coadministering agents that provide prophylaxis against common toxicities, and 4) coadministering other effective anticancer agents. Clinical trials testing most of these strategies have been completed or are under way. The National Cancer Institute has a substantial research portfolio dedicated to the identification, testing, and development of NSAIDs as preventive and therapeutic anticancer agents. Discovering how to apply NSAIDs in persons with—or at risk for—cancer, although challenging, has the potential for considerable clinical and public health benefits.

From the Gastrointestinal & Other Cancers Research Group, National Cancer Institute, Division of Cancer Prevention, Bethesda, Maryland, U.S.A.

This work was prepared in our capacity as employees of the U.S. federal government.

Address correspondence and reprint requests to Dr. Ernest T. Hawk, National Cancer Institute, Division of Cancer Prevention, EPN, Suite 2141, 6130 Executive Boulevard, Bethesda, MD 20892-7317, U.S.A.;

© 2003 Lippincott Williams & Wilkins, Inc.