Prostate Cancer Prevention Study Shows No
Benefit
for Use of Selenium and Vitamin E Supplements
Initial, independent review of study data from the Selenium
and Vitamin E Cancer Prevention Trial (SELECT), funded by
the National Cancer Institute (NCI) and other institutes that
comprise the National Institutes of Health shows that selenium
and vitamin E supplements, taken either alone or together,
did not prevent prostate cancer. The data also showed two
concerning trends: a small but not statistically significant
increase in the number of prostate cancer cases among the
over 35,000 men age 50 and older in the trial taking only
vitamin E and a small, but not statistically significant increase
in the number of cases of adult onset diabetes in men taking
only selenium (10 percent for those taking selenium vs. 9.3
percent taking placebo). Neither of these findings proves
an increased risk from the supplements and both may be due
to chance.
The Southwest Oncology Group (SWOG), an international network
of research institutions, coordinates SELECT at more than
400 clinical sites in the United States, Puerto Rico, and
Canada.
Data and additional analyses of the SELECT trial were published
online December 9, 2008, in JAMA. Among the specific results
highlighted, the five-year rate of prostate cancer diagnosis
in the four arms of the study was 4.43 percent in the placebo
arm of the trial, 4.56 percent in the selenium arm, 4.93 percent
in the vitamin E arm (the highest rate, but one that does
not show a statistically significant difference from the placebo
arm), and 4.56 percent in the selenium plus vitamin E arm.
Adherence to the study protocol dropped off from year one
to year five (83 percent adherent vs. 65 percent at year five),
which was expected and did not affect the trial outcome.
SELECT participants received letters in October 2008 explaining
the study review and telling them to stop taking their study
supplements. Participants will continue to have their health
monitored by study staff, which may include regular digital
rectal exams and PSA (prostate-specific antigen) tests to
detect prostate cancer. Investigators intend to follow the
participants for about three years to determine the long-term
effects of having taken either supplement or placebo and to
complete a biorepository of blood samples that will be used
in extensive molecular analyses to give researchers a better
understanding of prostate cancer, other cancers, and other
diseases of male aging. This additional data collection is
a vital part of the study.
 Neither
the men nor their physicians know which supplements or placebos
the men have been taking, a procedure known as blinding or
masking. As followup of the SELECT participants continues,
the participants will continue to be blinded. A blinded followup
may avoid unintentional bias and potentially false conclusions.
However, at the request of a participant, they will be informed
which supplement, if any, they received.
“SELECT was always designed as a study that would answer
more than a single question about prostate cancer,”
said Eric Klein, M.D., a study co-chair for SELECT, and a
physician at the Cleveland Clinic. “As we continue to
monitor the health of these 35,000 men, this information may
help us understand why two nutrients that showed strong initial
evidence to be able to prevent prostate cancer did not do
so.”
SELECT was undertaken to substantiate earlier, separate findings
from studies in which prostate cancer was not the primary
outcome: a 1998 study of 29,133 male smokers in Finland who
took vitamin E to prevent lung cancer surprisingly showed
32 percent fewer prostate cancers in men who took the supplement,
and a 1996 study of 1,312 men and women with skin cancer who
took selenium for prevention of the disease showed that men
who took the supplement had 52 percent fewer prostate cancers
than men who did not take the supplement.
Based on these and other earlier findings, in 2001, men were
recruited to participate in SELECT. They were randomly assigned
to take one of four sets of supplements or placebos, with
more than 8,000 men in each group. One group took both selenium
and vitamin E; one took selenium and a vitamin E placebo;
one took vitamin E and a selenium placebo; and the final group
received placebos of both supplements.
It should be noted that in 2003, while SELECT was recruiting
men, a different SWOG-sponsored study reported that the drug
finasteride reduced the incidence of prostate cancer by 25
percent. When this was discovered, men on SELECT were informed
and allowed to take finasteride (4.8 percent of men, not on
the other SWOG study, took the drug at some time during the
SELECT trial). Finasteride has not yet been approved by the
U.S. Food and Drug Administration for prostate cancer prevention.
Except for skin cancer, prostate cancer is the most common
type of cancer in men in the United States. In 2008, there
will be an estimated 186,320 new cases of prostate cancer
and 28,660 deaths from this disease in the United States.
“Finding methods to prevent and treat prostate cancer
remains a priority for the NCI, and with the aid of new molecular
diagnostic tools and applications, we hope to continue to
make headway in reducing deaths and new cases of this disease,”
said NCI director John E. Niederhuber, M.D. “The science
of cancer prevention is also leading toward individualized,
molecular prevention, in which we will calculate risk and
design preventive steps based on an individual's genome.”
SELECT has been funded by NCI for $114 million, with additional
monies from the National Center for Complementary and Alternative
Medicine, and with substudies funded and conducted by the
National Heart, Lung and Blood Institute, the National Institute
of Aging and the National Eye Institute at NIH. The substudies
were evaluating the effects of selenium and vitamin E on chronic
obstructive pulmonary disease, the development of Alzheimer's
disease, and the development of macular degeneration and cataracts,
and will continue without participants taking study supplements.
An NCI-funded substudy is looking at the effects of the supplements
on men who developed colon polyps.
“The SELECT trial owes a tremendous debt to our volunteers,
the thousands of men who offered their time and enthusiastic
participation, all in the interest of a future when prostate
cancer can be prevented,” said Laurence H. Baker, D.O.,
chairman of the Southwest Oncology Group. SELECT investigators
are analyzing the data and will submit the analysis for publication
in a peer-reviewed medical journal.
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