Rescuing COX-2 Inhibitors From the Waste Bin

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Abstract
COX-2 inhibition has been a main target for new nonsteroidal anti-inflammatory drug (NSAID) development. The effectiveness of two COX-2–specific drugs, Vioxx (rofecoxib) from Merck and Celebrex (celecoxib) from Pfizer, in chronic inflammatory diseases such as arthritis, was so highly promoted that they were among the most prescribed drugs in the category; experimental studies also showed promise in other diseases, including cancer ( 1 ) . Both drugs have recently met criticism. Vioxx was voluntarily pulled off the market in September 2004 by Merck and recently returned with cautions; a threefold higher relative risk of mortality from cardiovascular complications as compared with older non–COX-2–selective NSAIDs was reported ( 2 , 3 ) . After optimistic publicity by Pfizer but controversial clinical trial results, the consumer advocate group Public Citizen requested that Celebrex and its close cousin Bextra (valdecoxib) be withdrawn. We suggest that clues to the origin of the cardiovascular side effects come from the area of cancer research, in which COX-2 inhibitors are being tested for chemoprevention ( 1 ) .