Colorectal cancer (CRC) is a serious yet preventable disease. The low acceptance and cost of colonoscopy as a screening method or CRC make
chemoprevention an important option. Nonsteroidal anti-inflammatory drugs (
NSAIDs), not currently recommended for CRC prevention, have the potential to evolve into the agents of choice for this indication. Here, we discuss the promise and challenge of
NSAIDs for this chemopreventive application.Multiple epidemiologic studies, randomized clinical trials (RCTs) of sporadic colorectal
polyp recurrence, RCTs in patients with hereditary
colorectal cancer syndromes, and pooled analyses of cardiovascular-prevention RCTs linked to
cancer outcomes have firmly established the ability of conventional
NSAIDs to prevent CRC.
NSAIDs, however, are seriously limited by their toxicity,which can become cumulative with their long-term administration for
chemoprevention, whereas drug interactions in vulnerable elderly patients compound their safety. Newer, chemically modified
NSAIDs offer the hope of enhanced efficacy and safety.Recent work also indicates that targeting earlier stages of colorectal
carcinogenesis, such as the lower complexity
aberrant crypt foci, is a promising approach that may only require relatively short use of chemopreventive agents.
Drug combination approaches exemplified by
sulindac plus
difluoromethylornithine appear very efficacious. Identification of those at risk or most likely to benefit from a given intervention using predictive
biomarkers may usher in personalized
chemoprevention. Agents that offer simultaneous
chemoprevention of diseases in addition to CRC, e.g., cardiovascular and/or
neurodegenerative diseases,may have a much greater potential for a broad clinical application.