Chemoprevention is the use of agents to slow progression of, reverse, or inhibit
carcinogenesis thereby lowering the risk of developing invasive or clinically significant disease. With its long latency, high incidence and significant morbidity and mortality,
prostate cancer is a relevant target for
chemoprevention. Developing rational chemopreventive strategies for
prostate cancer requires well-characterized agents, suitable cohorts, and reliable intermediate
biomarkers of
cancer. Chemopreventive agent requirements are experimental or epidemiologic data showing efficacy, safety on chronic administration, and a mechanistic rationale for activity. Current promising agents include
antiandrogens and
antiestrogens;
steroid aromatase inhibitors;
retinoids and their modulators; 5alpha-reductase inhibitors;
vitamins D, E, and analogs;
selenium compounds;
carotenoids; soy
isoflavones; dehydroepiandrostenedione and analogs; 2-
difluoromethylornithine;
lipoxygenase inhibitors; apoptosis inducers; and nonsteroidal anti-inflammatory drugs. Identifying
biomarkers and validating them as
surrogate endpoints for
cancer incidence are critical for prostate
chemoprevention trials. Potentially useful
biomarkers for prostate
chemoprevention are associated with histologic, proliferative, differentiation-related, biochemical, and genetic/regulatory features of
prostatic disease. In that the prostate is not easily visualized, critical issues also include adequacy and consistency of tissue sampling. Various drugs for the
chemoprevention of
prostate cancer are now under evaluation in phase 1, 2, and 3 clinical trials. Cohort selection should be based on various patient characteristics (stage of the disease, previous
cancers or premalignant lesions, or high risk factors) and should be conducted within the context of standard treatment.