Nonsteroidal anti-inflammatory drug use and sporadic colorectal adenomas

First, and most importantly, the standard of care for treating adenomatous polyps is polypectomy and not therapy with NSAIDs. The initial clinical observation by Waddell and Loughry in 1983 that sulindac treatment influenced rectal polyps in patients with FAP has led to a considerable amount of research, commentary, and discussion during the past decade. These original observations have been validated by controlled clinical trials. Work presented in this issue by Ladenheim et al. indicates that sulindac may not be effective therapy for sporadic polyps that are present before initiation of treatment (secondary prevention). Even though their study may have failed to show a small effect of NSAIDs on polyps, further investigation of the ability of NSAIDs to cause regression of established polyps is probably not warranted. A more clinically relevant question, whether or not these agents can be used in a primary prevention strategy to prevent the development of adenomas in a colon devoid of these lesions, is currently being addressed in a large trial with sufficient statistical power to render firm conclusions (personal communication, January 1995). The multiple reports that sulindac treatment causes regression of adenomas in patients with FAP has stimulated research directed at understanding the molecular basis for these effects. If we are able to understand the molecular mechanism by which NSAIDs decrease the risk of colorectal cancer, we might be able to design more effective drugs or other approaches that would be clinically useful in humans for colorectal cancer chemoprevention.