Prostate cancer chemoprevention represents a relatively new and promising strategy for reducing the immense public health burden of this devastating
cancer of men in the United States and Western societies.
Chemoprevention is defined as the administration of agents (drugs, biologics, and natural products) that modulate (inhibit) one or more steps in the multistage
carcinogenesis process culminating in invasive
adenocarcinoma of the prostate. In 2000, there were an estimated 170,000 new cases of
prostate cancer and 31,000 deaths in the United States. During the past decade, the National Cancer Institute (NCI) organized the
chemoprevention research program and began testing the first generation of promising agents (eg, 4-(hydroxy)-
fenretinide [4-HPR],
difluoromethylornithine [DFMO],
antiandrogens) in high-risk cohorts and launched the first-large scale US phase 3 primary prevention trial, known as
Prostate Cancer Prevention Trial (PCPT-1), in 18,000 average-risk men (age more than 55 years and
prostate-specific antigen [PSA] less than 3 ng/mL) treated for 7 years with
finasteride or placebo. In the summer of 1998, the NCI
Prostate Cancer Progress Review Group (PRG) Report to the director of NCI was published in response to the leadership of the
prostate cancer advocacy community in conjunction with Congress. To further elucidate and address critical issues identified in this report and to develop a research agenda for the newly created Prostate and
Urologic Cancer Research Group in the Division of
Cancer Prevention at NCI, the NCI organized the workshop "New Clinical Trial Strategies for
Prostate Cancer Chemoprevention." The major objectives were to promote understanding and cooperation among the NCI, US Food and Drug Administration (FDA), academia, pharmaceutical industry, and the public regarding new opportunities for clinical prevention trials for
prostate cancer. The workshop was divided into three concurrent breakout panels and a fourth joint integrative panel. The workshop addressed multiple key areas identified in the PRG report in the following panels: (1) Molecular Targets and Promising Agents in Clinical Development; (2) Intermediate Endpoint
Biomarkers for Prevention Trials; (3) High-Risk Study Populations for Prevention Trials, and (4) Preventive Clinical Trial Designs and Regulatory Issues. Expert panelists were drawn from leading academic,
pharmaceutical, and government scientists in basic research and clinical investigation. Key
pharmaceutical, biotechnology, academic, and National Institutes of Health scientists presented overviews of their new agents and products in clinical development (representing the next generation of promising agents). Senior FDA physicians from the Center for Drugs and Center for Biologics presented on current standards for new
drug and
biologic approval for
chemoprevention efficacy. Some of the key topics included recent advances in the state of knowledge of promising agents in the clinic based on molecular targets as well as bottlenecks in
drug development for
pharmaceutical sponsors; strategic modulable
biomarkers that can serve as primary endpoints in phase 1/2 trials to assess preventive efficacy; high-risk cohorts with precancer (high-grade
prostatic intraepithelial neoplasia) and representative clinical trial designs that are ready for immediate translation into efficient prevention trials, such as Bayesian sequential monitoring for early assessment of
biologic activity and factorial designs for assessment of multiagent combinations. Finally, each expert panel generated recommendations for areas of future research emphasizing opportunities and infrastructure needs.