Executive summary of the National Cancer Institute Workshop: Highlights and recommendations

Prostate cancer chemoprevention represents a relatively new and promising s trategy for reducing the immense public health burden of this devastating c ancer of men in the United States and Western societies, Chemoprevention is defined as the administration of agents (drugs, biologics, and natural pro ducts) that modulate (inhibit) one or more steps in the multistage carcinog enesis process culminating in invasive adenocarcinoma of the prostate. In 2 000, there were an estimated 170,000 new cases of prostate cancer and 31,00 0 deaths in the United States. During the past decade, the National Cancer Institute (NCI) organized the chemoprevention research program and began te sting the first generation of promising agents leg, 4-(hydroxy)-fenretinide [4-HPR], difluoromethylornithine [DFMO], antiandrogens in high-risk cohort s and launched the first-large scale US phase 3 primary prevention trial, k nown as Prostate Cancer Prevention Trial (PCPT-1), in 18,000 average-risk m en (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 19 98, the NCI Prostate Cancer Progress Review Group, (PRC) Report to the dire ctor of NCI was published in response to the leadership of the prostate can cer advocacy community in conjunction with Congress. To further elucidate a nd address critical issues identified in this report and to develop a resea rch agenda for the newly created Prostate and Urologic Cancer Research Grou p in the Division of Cancer Prevention at NCI. the NCI organized the worksh op "New Clinical Trial Strategies for Prostate Cancer Chemoprevention." The major objectives were to promote understanding and cooperation among the N CI, US Food and Drug Administration (FDA), academia, pharmaceutical industr y, and the public regarding new opportunities for clinical prevention trial s for prostate cancer. The workshop was divided into three concurrent break out panels and a fourth joint integrative panel. The workshop addressed mul tiple key areas identified in the PRC report in the following panels: (1) M olecular Targets and Promising Agents in Clinical Development; (2) Intermed iate Endpoint Biomarkers for Prevention Trials; (3) High-Risk Study Populat ions for Prevention Trials, and (4) Preventive Clinical Trial Designs and R egulatory Issues. Expert panelists were drawn from leading academic, pharma ceutical, and government scientists in basic research and clinical investig ation. 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 agen ts). Senior FDA physicians from the Center for Drugs and Center for Biologi cs presented on current standards for new drug and biologic approval for ch emoprevention 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 spon sors; strategic modulable biomarkers that call serve as primary endpoints i n phase 1/2 trials to assess preventive efficacy; high-risk cohorts with pr ecancer (high-grade prostatic intraepithelial neoplasia) and representative clinical trial designs that are ready for immediate translation into effic ient prevention trials, such as Bayesian sequential monitoring for early as sessment of biologic activity and factorial designs for assessment of multi agent combinations. Finally, each expert panel generated recommendations fo r areas of future research emphasizing opportunities and infrastructure nee ds. (C) 2001, Elsevier Science Inc.