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Finasteride
(Proscar) Fails
to Prevent Prostate Cancer
In Men At High Risk
May Increase Risk For Men With PIN
August 1, 1998 A new study by USC/Norris Cancer Center
raises questions about the potential use of the drug finasteride to prevent
prostate cancer. Although this study is small, the researchers say the
results may be significant.
Scientists have thought that finasteride,
sold under the brand name Proscar and commonly used to treat benign prostate
disease (BPH), might offer men a way to cut their risk of developing prostate
cancer. Yet, "it appears that finasteride may not be effective as
a chemopreventive agent against prostate cancer, at least in men with
high PSA levels," says Ronald K. Ross, M.D., USC professor of preventive
medicine and deputy director of the USC/Norris Cancer Center.
"There may even be a subgroup of patients
in whom the drug actually could be harmful," says co-author Richard
J. Cote, M.D., USC associate professor of pathology and urology. Ross
and Cote, along with Eila C. Skinner, M.D., USC associate professor of
urology, led the study, published August 1998 in The British Journal
of Cancer.
USC/Norris researchers have done leading work on the role of the
male hormones (androgens) in spurring prostate cancer growth. Ross and
colleagues proposed that lowering levels of the androgen most active in
the prostate, called dihydrotestosterone (DHT), might prevent prostate
cancer.
Finasteride lowers the levels of DHT by
blocking the enzyme that converts testosterone into DHT. Ross's team was
the first to suggest that this action might prevent the formation of prostate
cancer. This makes it all the more significant to see them now express
serious doubt.
The National Cancer Institute (NCI) is in
the midst of a large national clinical trial to determine if finasteride
can reduce the incidence of prostate cancer. The seven-year NCI study
has enrolled more than 18,000 healthy men with normal PSA levels.
Finasteride, manufactured by Merck & Co.,
is used to shrink the enlarged prostate glands of men with benign prostate
hyperplasia (BPH) and improve symptoms. A lower dose of finasteride was
approved by the FDA last year to treat hair loss in men (male pattern
baldness), and is marketed under the brand name Propecia.
"Ours are the first data to address
the question of whether finasteride prevents disease. The results are
not reassuring," Ross says. In contrast to the NCI study (which is
focusing on healthy men), the USC team studied 52 men with elevated blood
levels of PSA (prostate specific antigen) whose biopsies showed no signs
of prostate cancer. PSA is a protein produced only by prostate cells.
Doctors use it as a broad, though fallible, screening marker for prostate
cancer.
Because all of the men in this study had
elevated PSA levels, they were considered to have a higher risk of developing
prostate cancer than men with normal PSA levels. Half of the men were
treated with finasteride (Proscar) for one year, while the other half
received no treatment.
At the end of the study, a second biopsy
revealed that eight of the 27 men who took finasteride had developed tumors,
compared to only one of the 25 men in the group that had taken nothing.
To evaluate the drug's ability to block
tumor development, Cote, Ross and Skinner tracked key intermediate markers
of disease, a novel approach to testing new chemopreventive agents. They
measured the participants' blood levels of testosterone, PSA and dihydrotestosterone
(DHT); they also compared tissue samples from the biopsies at the start
of the study to those at the end.
While men in the control group showed no
changes in blood levels of PSA, testosterone, or dihydrotestosterone,
the treated men's PSA levels dropped by 48% and dihydrotestosterone levels
fell by 67%. However, men in the treatment group saw their testosterone
levels rise by 21% during the study.
The team also looked at tissue samples for
a marker of benign disease (hyperplastic epithelial tissue) and two markers
associated with increased risk of prostate cancer  the presence of precancerous
lesions known as PIN (prostate intraepithelial neoplasia) and the rate
of cell proliferation in the prostate gland. They found that, as expected,
finasteride reduced the proportion of the hyperplastic epithelial tissue.
But, the drug had no effect on PIN or proliferation, which are more strongly
linked to the development of cancer.
The results suggest that although finasteride
lowers DHT levels, the net effect of hormones acting on the prostate may
be unchanged by the drug, Ross says. That may be because of rising testosterone
levels in the men taking finasteride. Although not as potent as DHT, testosterone
can also spur prostate cell growth.
"The biology is not as straightforward
as many people have assumed," Ross concludes. Notably, of the eight
men who had precancerous lesions at the start of the study and were treated
with finasteride, six developed cancer after one year. In comparison,
in the no-treatment group, none of the five men with precancerous lesions
got cancer. This finding, though in a small sub-group of the men, was
statistically significant. It led the researchers to state: "finasteride
is unlikely to be useful and may even be harmful in men with PIN."
"If finasteride were to have had an
anti-cancer effect, it is likely that it would have showed up in these
patients," Ross says. The USC team holds off, however, on predicting
the results of the national trial. "It is possible that the drug
could have a beneficial effect in preventing prostate cancer in some men,
though the results of this study suggest that this is unlikely,"
Ross says.
Richard J. Cote, Eila C. Skinner, Carol E. Salem, Susan J. Mertes,
Frank Z. Stanczyk, Brian E. Henderson, Malcolm C. Pike, and Ronald K.
Ross. "The effect of finasteride on the prostate gland in men with
elevated serum prostate specific antigen (PSA) levels." British Journal
of Cancer, 78 (3) August 1998.
Low dose finasteride, sold on prescription under the brand
name Propecia for treating male hair loss, is not for use by women or
children. Women must especially avoid contact with it if they are or may
be pregnant because it can cause abnormalities of the male baby's sex
organs. See FDA Clears
Propecia for Treatment of Hair Loss in Men
August 3, 1998. Page last modified December 30, 1998
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