Best Leads for Prostate Cancer Prevention Appear in April Urology Supplement; Agents, Biomarker Endpoints, Cohorts, and Trial Designs Outlined
The most promising agents to prevent prostate cancer and the most likely biological markers of risk for the disease are just two of the key areas of prostate cancer prevention research highlighted in the supplement to the April issue of the journal Urology, "New Clinical Trial Strategies for Prostate Cancer Prevention." Capturing the recent advances in the converging fields of cancer chemoprevention and preventive urologic oncology, the science published in this journal aims to stimulate and guide research in this crucial area.
The supplement originated in a workshop conducted by the National Cancer Institute (NCI) in August 1999, and the information was updated as the publication went to press. The papers in the supplement contain the latest information on:
- Agents: which drugs and supplements are candidates for prostate cancer prevention, including anti-androgens, anti-estrogens, retinoids, COX-2 inhibitors and other non-steroidal anti-inflammatory drugs, differentiation agents, tyrosine kinase inhibitors, and anti-oxidants (See Table I in the Executive Summary);
- Biomarkers: the major classes of biological markers of prostate cancer risk and how they might be used as intermediate endpoints in trials, including cell changes, markers of DNA damage, and tissue-specific markers like prostate-specific antigen (PSA) (See Table III in the Executive Summary);
- Cohorts: what populations should be included in prevention studies due to their increased risk of developing the disease, including those with family history, known dysplasia (abnormal growth in the prostate), elevated PSA, or certain inherited genetic changes (See Table V in the Executive Summary); and
- Designs: what kind of prevention trials could be conducted quickly and with a minimum number of individuals to find out what agents and biomarkers work best (See Table VIII in the Executive Summary).
"Cancer is not a single event, but the result of a long process," said Peter Greenwald, M.D., Dr. P.H., director of NCI's Division of Cancer Prevention. "We are working to identify the points in the process of prostate cancer development where we can jump in and stop it. We need to find agents vitamins, minerals, or drugs that will stop the cancer process. And we need to find markers that both let us know someone is at risk for cancer and let us know that the agents that person is taking are, in fact, reducing that risk."
NCI has two large-scale trials under way for prostate cancer prevention: the Prostate Cancer Prevention Trial, started in 1993, is testing the drug finasteride vs. a placebo in 18,000 men. Results are expected in 2003. SELECT, the Selenium and Vitamin E Cancer Prevention Trial is gearing up to open this summer, and will look at selenium, vitamin E, and both supplements together vs. a placebo in 32,400 men.
Such large-scale trials are rare and are undertaken only when evidence is clear that they are the only way to answer a crucial research question. NCI is also conducting smaller trials with a variety of agents, including a vitamin D analog; eflornithine (a compound called DFMO); Flutamide and Casodex (both anti-androgens); soy isoflavones; lycopene (a plant pigment common in tomatoes); selenium; celecoxib (a COX-2 inhibitor); and combinations of agents.
The kinds of trials outlined in the supplement are key stepping stones to large, definitive trials. "Trials like the PCPT and SELECT will give us vital information about how to prevent prostate cancer, but more work is necessary," said Greenwald.
Prostate cancer is the second most frequently diagnosed cancer in U.S. men (next to nonmelanoma skin cancer) and the second leading cause of cancer death. Black men in the United States have the highest rates of prostate cancer in the world.
The entire supplement is available online beginning today (April 9, 2001) at:
Choose "The Journal" button and look under "Previous Issues."
Reporters can also obtain a copy of the Executive Summary from:
NCI Press Office, (301) 496-6641
Elsevier Publishing at (212) 462-1933.