Prostate cancer has been the most common visceral
malignancy in American men for the last decade. The estimated lifetime risk of
the disease in the United States is 16.6% for white men and 18.1% for
African-American men, with a lifetime risk of death of 3.5% and 4.3%,
respectively. Recently, the National Cancer Institute (NCI) reported that the
overall cancer mortality rate decreased between 1990 and 1997, including a
reduction of approximately 6% in prostate cancer mortality. Furthermore,
Tarone et al reported that the mortality rate for prostate cancer among white
men in the United States declined to a level lower than that reported prior to
the introduction of prostate-specific antigen (PSA)-based screening in 1987.
These improvements in mortality have been variously ascribed to screening,
improvements in therapeutic modalities, earlier and more aggressive therapy, and
more appropriate application of hormone manipulation. However, marked
disparities in prostate cancer incidence and mortality among various ethnic
groups in the United States and around the world highlight the relative lack of
knowledge of the genetic, environmental, nutritional, and biological variables
important to this disease.[3,4]
Moreover, despite these advances, most men who develop metastatic disease are
destined to die of prostate cancer. An ideal method of reducing the mortality
and morbidity associated with carcinoma of the prostate would be through primary
prevention; ie, either by reducing the number of life-threatening, clinically
evident cases or the age-dependent rate of development so that tumors would
become evident 5, 10, or 15 years later. As illustrated in the article by
Drs. Das and Kaplan, the use of nontraditional dietary supplements is widespread
among men with prostate cancer and those who perceive themselves to be at risk,
and the willingness to use such agents provides a ripe opportunity for
conducting well-controlled clinical trials of these agents.
The Prostate Cancer Prevention Trial
The recognition that the androgenic milieu of the prostate was important in
the development of prostate cancer led to the Prostate Cancer Prevention Trial,
or PCPT (Southwest Oncology Group [SWOG]-9217), an investigation of finasteride
(Proscar). A testosterone analog, finasteride competitively inhibits the enzyme
5-alpha reductase (type 2)which converts testosterone to dihydrotestosterone
(DHT) in the prostateand causes a profound reduction in circulating and
cellular DHT. Finasteride inhibits the growth of prostate cancer cells in
vitro and is an active preventive agent in certain prostate-carcinogenesis
The PCPT is an ongoing phase III, double-blind, placebo-controlled,
randomized trial to determine the efficacy of finasteride in reducing the
prevalence of prostate cancer. This trial opened in 1993 and easily exceeded the
goal of 18,000 randomized men during the planned 3-year accrual period, a fact
that demonstrates broad public support for chemoprevention efforts. Men enrolled
in the PCPT are currently undergoing end-of-study prostate biopsies, and results
are expected in 2004.
Selenium as a Chemopreventive
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rates in assessing recent declines in prostate cancer mortality rates.
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8. Heinonen OP, Albanes D, Huttunen JK, et al: Prostate cancer and
supplementation with alpha-tocopherol and beta-carotene: Incidence and mortality
in a controlled trial. J Natl Cancer Inst 90:440-446, 1998.
9. Clark LC, Dalkin B, Krongrad A, et al: Decreased incidence of prostate
cancer with selenium supplementation: Results of a double-blind cancer
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10. The ATBC Cancer Prevention Study Group: The effect of vitamin E and
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cancer prevention trial. J Urol 166:1311-1315, 2001.