Evolving strategies for prostate cancer chemoprevention trials.

Prostate cancer chemoprevention (CP) can be defined as the use of natural and synthetic agents that inhibit, reverse or regress precancer and delay progression to invasive cancer. During the past two decades several CP strategies have evolved. The first generation of CP trials tested the efficacy of antioxidants and vitamins including B-carotene, vitamin A, retinol, 13 cis retinoic acid, vitamins E, C and selenium. Although these trials were disappointing, provocative hypotheses were generated for selenium and vitamin E that set the stage for future prostate trials. In the 1990s, the NCI launched a second generation of large CP trials aimed at breast and prostate cancer. One of these trials is the PCPT, testing the efficacy of a 5 alpha-reductase inhibitor-finasteride to prevent prostate cancer in 18,000 men. Although PCPT is still in progress, the NCI recently launched a second large primary prostate CP trial called SELECT, testing the efficacy of selenium and vitamin E in 32,400 men. The Prostate Cancer Progress Report to the Director of NCI in 1998 challenged the research community to design more efficient CP trials for prostate cancer. In response, the NCI has evolved a third generation of CP trials. This involves pharmacologically driven translational science research including agents and their targets, biomarker endpoints, suitable clinical models for testing agents and efficient trial designs employing high risk cohorts and surrogate endpoints. In summary, a dual strategy for CP is being developed which includes public health measures and a medical intervention approach.