Colorectal cancer (CRC) is among the most common human
malignancies and remains a leading cause of
cancer-related morbidity and mortality. Colorectal
carcinogenesis is a multistep process characterized by molecular and cellular alterations that result in an identifiable precursor lesion, ie, the
adenomatous polyp. The transition from normal mucosa to
adenoma and its subsequent progression to
carcinoma are protracted events that offer opportunities for preventive interventions. Suppression or reversal of the carcinogenic process in the colorectum with nonpharmacologic or pharmacologic agents, ie,
chemoprevention, is an area of considerable research interest and activity. Interest in this field derives from multiple epidemiologic studies showing that regular and continued use of nonsteroidal anti-inflammatory drugs (
NSAIDs), predominantly
aspirin, is associated with significant reductions in both colorectal
adenoma and
carcinoma incidence.
NSAIDs were first shown to be effective in patients with
familial adenomatous polyposis (FAP). Subsequent randomized trials in FAP demonstrated that
sulindac and the selective
cyclooxygenase-2 (COX-2) inhibitor,
celecoxib, can significantly regress existing
adenomas, and resulted in Food and Drug Administration (FDA) approval of
celecoxib for adjunctive management of these patients. Based on the aforementioned data,
aspirin and
coxibs have been or are currently being evaluated for the prevention of sporadic
adenoma recurrence in high-risk patient populations. Evidence indicates that
aspirin can reduce
adenoma recurrence rates in patients with prior colorectal
neoplasia; however, questions remain, including the optimal dosage, timing of initiation and
duration of treatment, and clinical benefit versus potential harm to patients. These same issues apply to the nonpharmacologic agents such as
calcium,
folic acid, and
selenium given as dietary supplements. Apart from
aspirin,
calcium carbonate is the only other agent that has been shown to modestly reduce sporadic
adenoma recurrence rates in a randomized trial.
Folate and
selenium are being actively studied based on provocative preclinical data. In addition to demonstrating efficacy, chemopreventive agents must also be safe for long-term use, be well accepted by patients, and be cost-effective. In this review, the current status of CRC
chemoprevention will be discussed, including the available evidence for selected pharmacologic and nonpharmacologic agents, particularly among high-risk populations.