The role of chemoprevention in cancer control.

Chemoprevention is a promising strategy for cancer prevention that is international in application and may be more immediate in worldwide impact than either dietary modification or prevention of exposure to carcinogens. Precedent for a chemopreventive approach is found in cardiology, where cholesterol-lowering, antihypertensive and antiplatelet agents are administered to prevent heart disease progression in high-risk individuals. The multistep nature of carcinogenesis provides many opportunities for chemopreventive interventions with agents targeted to specific mechanisms involved in cancer initiation, promotion and progression. The well-defined strategy for development of chemopreventive agents includes evaluation of leads from epidemiological and experimental research; preclinical efficacy testing of candidate agents; and assessments of the preclinical and clinical safety, toxicity, bioavailability and pharmacokinetics of those that are the most promising. Short-term clinical trials then determine optimal dosing and characterize the efficacy of the best agents against intermediate biomarkers of cancer. Large-scale randomized trials, the final stage of this strategy, evaluate whether the chemopreventive agents actually do reduce cancer risk. The systematic development of agents is coupled with basic research into mechanisms of action and subsequent application of the findings to agent design and discovery. Major objectives of chemopreventive drug development include identification and validation of intermediate biomarkers that are accurate predictors of future cancer incidence and that can serve as surrogate and points for clinical disease. Complementary international efforts to standardize chemopreventive trial designs and protocols among communities worldwide would help ensure a valid comparison of results across countries and more efficient and effective cancer-preventive regimens.