The SELECT Trial: Selenium, Vitamin E and Prostate Cancer Prevention
Based on the “Selenium and Vitamin
E Cancer Prevention Trial (SELECT): Questions and Answers” page of the
National Cancer Institute website
Edited (with Introduction) by Dr. Don Rose, Writer,
Life Alert
--
Studies have indicated that antioxidants can help
fight and prevent disease, including cancer. Hence, many people take them as daily
dietary supplements. This is especially relevant for
seniors,
who often experience a drop in antioxidant levels as they age. This article discusses
a clinical trial called SELECT, designed to determine whether two popular antioxidants
– selenium and Vitamin E – can prevent prostate cancer. While new enrollment in
this study has ended, the followup is still ongoing. Eventually, SELECT’s results
may yield important conclusions and recommendations to help in the battle to defeat
cancer. --Dr. Don Rose
--
Overview: Key Points
·
SELECT stands for the
Selenium and Vitamin
E
Cancer Prevention
Trial, a
clinical trial to see if one or both of these
dietary supplements prevent prostate cancer (see
Question 1).
·
Selenium and
Vitamin E are
antioxidants.
Earlier studies suggested that these supplements might prevent prostate cancer (see
Questions 3,
4, and
5).
·
In order to participate in
SELECT, men had to meet certain eligibility requirements (see
Questions 6,
7, and
8).
·
Men who participate in this
study were randomly assigned to take two capsules a day—selenium and vitamin E,
selenium and a
placebo, vitamin
E and a placebo, or two placebos (see
Question 10).
·
Participants are asked to
provide toenail and
blood samples,
respond to an annual questionnaire, and pick up capsules every 6 months (see
Question 13).
Questions and Answers
-
What is SELECT?
SELECT stands
for the Selenium
and Vitamin E
Cancer
Prevention Trial,
a clinical trial to see if one or both of these dietary supplements prevent prostate
cancer. The trial is funded by the National Cancer Institute (NCI) and is being
coordinated by the Southwest Oncology Group (SWOG), an international network of research institutions
that receives NCI funding. Enrollment began in 2001 and ended in 2004, 2 years ahead
of the originally planned 5 years. The study will continue for 7 years after the
last man enrolled, meaning that each man will participate for 7 years or more, depending
on when he joined the study. More than 400 sites in the
United States
, Puerto Rico, and
Canada
are taking part in the study. Over 35,000 men are participating
in SELECT.
-
What are a man’s
chances of developing prostate cancer?
Except for skin
cancer, prostate cancer is the most common type of cancer in men in the
United States
. In 2005, there will be an estimated 232,090 new cases
of prostate cancer and 30,350 deaths from this disease in the
United States
(1).
Approximately
1 in 6 men in the
United States
(or 17.8 percent) will develop prostate cancer during his
lifetime (1). All men are at risk, but those at highest risk fall into one or more
of the following categories: age 55 or older; black; or have a father or brother
with prostate cancer.
-
What is selenium?
Why study it for prostate cancer prevention?
Our bodies need selenium,
a nonmetallic trace element that we get from food—especially plant foods like
rice and wheat, seafood, meat, and Brazil nuts. Selenium is an antioxidant that
might help control cell
damage that can lead to cancer.
The Nutritional Prevention
of Cancer Trial, published in 1996, included 1,312 men and women who had skin cancer.
Men who took selenium to prevent nonmelanoma skin cancer received no benefit from selenium in preventing skin cancer.
However,
men who had taken selenium for 6½ years had approximately 60 percent fewer new cases
of prostate cancer than men who took the placebo
(2). In 2002, study data showed that men who took selenium for more than 7½ years
had about 52 percent fewer new cases of prostate cancer than men who took the placebo
(3). This study is one of the reasons selenium is being studied in SELECT. (See
Question 11 for more information about selenium.)
-
What is vitamin
E? Why study it for prostate cancer prevention?
We get vitamin
E in a wide range of foods, especially vegetables, vegetable oils, nuts, and egg
yolks. Vitamin E, like selenium, is an antioxidant, which might help control cell
damage that can lead to cancer.
In a 1998 study
of 29,133 male smokers in
Finland
, men who took vitamin E to prevent
lung cancer had 32 percent fewer new cases of
prostate cancer than men who took the placebo.
Some men also took beta carotene, but neither substance helped prevent lung cancer
(4). (See Question 12 for more information about vitamin E.)
-
What do researchers
hope to learn from SELECT?
SELECT is the first study to look directly at the effects of selenium and vitamin
E on the risk of prostate cancer. This study is designed to find out if selenium,
vitamin E, or both prevent prostate cancer.
A large trial of selenium
and vitamin E is needed to substantiate earlier, separate findings from studies
in which prostate cancer was not the primary outcome. Although two earlier studies
suggested that these two supplements might prevent prostate cancer, this cancer
was not the focus of those studies. The primary goal of SELECT is to assess the
effect of these substances on the number of new cases of prostate cancer diagnosed
during routine clinical practice. Other objectives are to assess the impact of selenium
and vitamin E on the incidence
of lung and colon cancer,
as well as on survival. SELECT will study the molecular
genetics
of cancer risk and associations between diet
and cancer. Additionally, SELECT will examine quality of life.
-
Who was eligible
to participate in SELECT? Were there restrictions on eligibility?
Many diseases, including
prostate cancer, occur more frequently in
older persons.
The risk of developing prostate cancer increases with age.
More than 92 percent of prostate cancer cases
occur in men age 55 and older.
Black men had
to be age 50 or older to participate, and men of other races and ethnicities had
to be 55 or older. The age for eligibility was lower for black men because, on average,
they get the disease at an earlier age. In addition, black men in the
United States
have the highest incidence of prostate cancer in the world.
Thus, the SELECT age requirement ensured that men at risk for the disease were the
ones who could enroll.
Men who had taken, or were
taking, vitamin E and/or selenium on their own had to stop using these supplements
and any multivitamins and use only what is provided by SELECT. These supplements
are provided to participants free of charge, including a multivitamin that does
not contain vitamin E or selenium. Past use of these supplements did not disqualify
men from joining SELECT.
Participants must have had
no history of prostate cancer. Men who joined SELECT also must not have had any
other cancer, except nonmelanoma skin cancer, in the last 5 years. They must have
been in generally good health. Many of the 18,000 men who participated in another
prevention study sponsored by NCI and run by SWOG, known as the Prostate Cancer
Prevention Trial (PCPT), were eligible to participate in SELECT if they had no evidence
of prostate cancer.
Some SELECT study sites are
located at Veterans Administration hospitals run by the Department of Veterans Affairs.
Veterans could enroll at these sites even if they did not receive their routine
medical care at that hospital.
-
Could men with benign prostatic hyperplasia (BPH) join SELECT?
Men with BPH, an
abnormal
growth of benign
prostate cells, could join SELECT because BPH is not a cancerous or
precancerous
condition. In BPH, the prostate grows larger and presses against the
urethra
and bladder,
interfering with the normal flow of urine. More than half of the men in the
United States
between the ages of 60 and 70, and as many as 90 percent
of men between the ages of 70 and 90, have
symptoms of BPH.
BPH can be treated with four
different FDA-approved drugs:
finasteride
(Proscar®), terazosin (Hytrin®), doxazosin (Cardura®), and tamsulosin (Flomax®).
Most men taking one of these drugs were eligible to participate in SELECT.
-
What tests were
used to determine eligibility for SELECT?
Tests included a
digital rectal examination (DRE)
and a prostate-specific antigen (PSA)
test. During a DRE, a doctor inserts a gloved finger into the
rectum
and feels the prostate gland
through the rectal
wall to check for bumps or abnormal areas. The PSA test measures the level of PSA
(a protein
produced by the cells of the prostate gland) in the blood. PSA levels can rise due
to cancer or benign (not cancerous) conditions. Doctors often use the PSA test and
DRE as prostate cancer screening tests in men who have no symptoms of the disease.
To be eligible for the SELECT
trial, participants had to have a DRE that found no signs of prostate cancer and
a total PSA level less than or equal to 4.0 ng/ml.
During the trial, DREs and
PSA tests are suggested, but not required, on an annual basis throughout the course
of the study.
-
Who pays for
these tests?
Physician,
medical examination, and general clinic costs, including DREs, are charged to the
participant in the same way as if he were not part of the trial. These costs may
be covered by a participant’s health insurance. Financial assistance may be available
for some men. SELECT, however, pays for follow-up PSA tests. Men with questions about insurance
coverage or reimbursement should check with their local SELECT site.
-
Who gets which
supplement?
Men who participate
in this study take two capsules a day. Participants were randomized (assigned by
chance) to receive:
·
selenium and vitamin E,
·
selenium and a placebo,
·
vitamin E and a placebo, or
·
two placebos.
Two types of
placebos are used in the trial: one looks and tastes like a selenium capsule; the
other looks and tastes like a vitamin E capsule. Each placebo contains only inactive
ingredients. Neither the participants nor the researchers will know who is receiving
the selenium and vitamin E, or the placebos, until the end of the study.
-
How much selenium
is being used in SELECT? What risks might be involved?
The amount of selenium (provided
as l-selenomethionine) is 200 ">micrograms (µg) daily. Although the initial results of
the Nutritional Prevention of Cancer Trial showed an overall decrease in cancer
incidence from selenium, a 2003 update reported 17 percent more new nonmelanoma
skin cancers in the selenium group compared with the placebo group (5). It is not
clear how these results would apply to men who did not already have skin cancer
when they enrolled in SELECT, or to men who are not at increased risk for skin cancer.
-
How much vitamin
E is being used in SELECT? What risks might be involved?
The amount of vitamin E (provided
as dl-alpha-tocopherol acetate) is 400 milligrams
(mg), which is equivalent to 400 International Units (IU)
per day. This dose
of vitamin E can thin the blood somewhat. Men with uncontrolled high blood pressure
were not eligible to take part in SELECT because taking this much vitamin E might
have increased their risk of stroke.
Vitamin E has been shown
to increase the risk of some cardiovascular conditions. In a 2005 study, men and women with vascular
disease or diabetes
who took 400 IU of vitamin E daily for 7 years had a 13 percent increased risk of
heart failure compared with participants taking a placebo (6). Heart failure is
a condition in which the heart’s ability to pump blood is weakened. A 2005
analysis
of several studies in which people with various medical problems took vitamin E
suggested a link between high doses of vitamin E (400 IU or more) and increased
mortality (7).
-
What other requirements
were there for SELECT participants?
Upon enrollment,
men were asked to have toenail clippings collected to assess selenium levels in
the body because selenium concentrates in fingernails and toenails. Toenails were
chosen over fingernails because they take longer to grow and thus contain more history
of someone’s selenium intake. Blood samples were collected upon enrollment to assess
levels of vitamin E.
Upon enrolling, men filled
out a questionnaire on their diet and past supplement use. There is also an annual
questionnaire that asks for updates of some of this information. Men do not have
to change their diets during this study.
Each man is offered a supply
of a special daily multivitamin that contains no selenium or vitamin E, to take
if he chooses. Vitamin E, selenium, placebo capsules, and multivitamins will be
provided free of charge to enrollees for the duration of the study. Participants
are asked to return to the study site every 6 months to pick up a 6-month supply
of capsules.
-
What are the
benefits of participating in SELECT?
Men involved
in SELECT are partners in medical research that may decrease their chances of getting
prostate cancer. Information learned from this study may also help future generations
of men avoid this cancer.
-
What happens
if a participant develops prostate cancer while involved in SELECT?
Participants
diagnosed with prostate cancer during the study will be referred for treatment,
will stop taking the study supplements, and will continue to be followed by the
SELECT study staff, although less frequently.
Costs for diagnosis
and treatment of prostate problems, prostate cancer, or other medical conditions
during the study are charged to the participant in the same way as if he were not
part of the trial. A participant’s insurance will pay for diagnosis and treatment
according to the plan’s policies. If the participant has no insurance, social services
may be available at the local level to cover costs for diagnosis and treatment.
-
What other clinical
trials are underway for prostate cancer prevention?
In addition to SELECT, smaller
trials are also being conducted with a variety of agents, including a vitamin D
analog;
soy
isoflavones;
and lycopene
(a plant pigment common in tomatoes).
-
Where is more
information about SELECT available?
In the
United States
and
Puerto Rico
, call the National Cancer Institute’s Cancer Information
Service at 1–800–4–CANCER (1–800–422–6237) for information in English or Spanish.
People with TTY equipment can call 1–800–332–8615 for information in English. In
Canada
, call the Canadian Cancer Society’s Cancer Information
Service at 1–888–939–3333 for information in English or French.
The following websites provide
additional information:
·
http://www.swog.org—choose the SELECT
option
·
http://www.cancer.gov/clinicaltrials/digestpage/SELECT—from the NCI
·
http://www.cancer.gov/newscenter/SELECT—provides images of
the prostate, the crystalline and chemical structures of vitamin E, and selenium
and vitamin E capsules
Selected References
-
American Cancer Society (2005).
Cancer Facts and Figures 2005.
Atlanta, GA
: American Cancer Society. Retrieved May 24, 2005, from
http://www.cancer.org/downloads/STT/CAFF2005f4PWSecured.pdf
-
Clark LC, Combs GF Jr., Turnbull BW, et al. Effects of
selenium supplementation for cancer prevention in patients with carcinoma of the
skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group.
Journal of the American Medical Association
1996; 276(24):1957–1963.
-
Duffield-Lillico AJ, Reid ME, Turnbull BW, et al. Baseline
characteristics and the effect of selenium supplementation on cancer incidence in
a randomized clinical trial: A summary report of the Nutritional Prevention of Cancer
Trial. Cancer Epidemiology, Biomarkers
& Prevention 2002; 11(7):630–639.
-
Heinonen OP, Albanes D, Virtamo J, et al. Prostate cancer
and supplementation with alpha-tocopherol and beta-carotene: Incidence and mortality
in a controlled trial. Journal of the
National Cancer Institute 1998; 90(6):440–446.
-
Duffield-Lillico AJ, Slate EH, Reid ME, et al. Selenium
supplementation and secondary prevention of nonmelanoma skin cancer in a randomized
trial. Journal of the National Cancer
Institute 2003; 95(19):1477–1481.
-
Lonn E, Bosch J, Yusuf S, et al. Effects of long-term vitamin
E supplementation on cardiovascular events and cancer: A randomized controlled trial.
Journal of the American Medical Association
2005; 293(11):1338–1347.
-
Miller ER III, Pastor-Barriuso R, Dalal D, et al. Meta-analysis:
High-dosage vitamin E supplementation may increase all-cause mortality. Annals of Internal Medicine
2005; 142(1):37–46.
Related Resources
Publications
Available at
www.cancer.gov/publications
:
·
National Cancer Institute Fact Sheet 5.23,
Early Prostate Cancer: Questions and Answers
·
National Cancer Institute Fact Sheet 5.29,
The Prostate-Specific Antigen (PSA) Test:
Questions and Answers
·
Taking Part
in Clinical Trials: Cancer Prevention Studies: What Participants Need To Know
·
Understanding
Prostate Changes: A Health Guide for All Men
·
What You Need
To Know About™ Prostate Cancer
The
SELECT Homepage
·
http://www.crab.org/select/
National
Cancer Institute (NCI) Resources
-
Cancer Information
Service (toll-free)
Telephone: 1–800–4–CANCER
(1–800–422–6237)
TTY: 1–800–332–8615
NCI’s Web site:
http://www.cancer.gov
LiveHelp,
NCI’s live online assistance:
https://cissecure.nci.nih.gov/livehelp/welcome.asp
This article is based on the webpage “Selenium and Vitamin
E Cancer Prevention Trial (SELECT): Questions and Answers” -- part of the
National Cancer Institute website. The information provided here is, to the
best of our knowledge, reliable and accurate. However, while
Life Alert
always strives to provide true, precise and consistent information, we cannot guarantee
100 percent accuracy. Readers are encouraged to review the original article, and
use any resource links provided to gather more information before drawing conclusions
and making decisions.
Dr. Don Rose writes books, papers and articles
on computers, the Internet, AI, science and technology, and issues related to seniors.
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