Introductory remarks: development of chemopreventive agents for prostate cancer.

The term "cancer chemoprevention" refers to the prevention of cancer by intervening with drugs prior to the malignant (i.e., invasive) stage of carcinogenesis. The development of chemopreventive drugs is the major objective of the Chemoprevention Branch at the National Cancer Institute. The testing of drugs for cancer chemoprevention differs from testing of those for cancer treatment. Chemopreventive drug trials involve healthy target populations, and the endpoints of reduced cancer incidence or mortality, reduced/eliminated precancerous lesions, or increased latency must be achieved with little or no drug toxicity. The design of cancer chemoprevention trials for prostate presents several problems, such as the age of the study population and undependable methods for detecting microscopic foci by sequential sampling. A major motivation for organizing this workshop is the development of strategies for the design of chemopreventive intervention trials for prostate cancer. One of the most difficult problems of chemoprevention drug testing is the necessity of lengthy trials due to the long developmental period of many cancers. This is especially true for prostate cancer. A major solution to the problem is the use of intermediate biomarkers, defined as morphological or molecular intraepithelial changes that can constitute short-term endpoints in chemoprevention clinical trials. They are categorized as histological, genetic, proliferation-related, and differentiation-related. Modulation of intermediate biomarkers, instead of cancer incidence, as trial endpoints would allow chemoprevention trials to be of shorter duration, to use fewer subjects, and to be of lower cost. Review of the current status of prostatic intermediate biomarkers, and methods for identifying and validating them, are also major reasons for convening this workshop.