Acents, biomarkers, and cohorts for chemopreventive agent development in prostate cancer

Chemoprevention is the use of agents to slow progression of, reverse, or in hibit carcinogenesis thereby lowering the risk of developing invasive or cl inically significant disease, With its long latency, high incidence and sig nificant morbidity and mortality, prostate cancer is a relevant target for chemoprevention. Developing rational chemopreventive strategies for prostat e 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 admi nistration, and a mechanistic rationale for activity. Current promising age nts include antiandrogens and antiestrogens; steroid aromatase inhibitors; retinoids and their modulators: 5 alpha -reductase inhibitors: vitamins D, E, and analogs; selenium compounds; carotenoids; soy isoflavones; dehydroep iandrostenedione and analogs; 2-difluoromethylornithine; lipoxygenase inhib itors: apoptosis inducers; and nonsteroidal anti-inflammatory drugs, Identi fying biomarkers and validating them as surrogate endpoints for cancer inci dence are critical for prostate chemoprevention trials. Potentially useful biomarkers for prostate chemoprevention are associated with histologic, pro liferative, differentiation-related, biochemical, and genetic/regulatory fe atures 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 eval uation in phase 1, 2, and 3 clinical trials. Cohort selection should he bas ed on various patient characteristics (stage of the disease, previous cance rs or premalignant lesions, or high risk factors) and should be conducted w ithin the context of standard treatment. (C) 2001, Elsevier Science Inc.