The Trial
1. What is the Prostate Cancer Prevention Trial?
The Prostate Cancer Prevention Trial, or PCPT, is a clinical chemoprevention
trial designed to see whether taking the drug finasteride (trade name
Proscar®) can prevent prostate cancer in men ages 55 and older. The study,
which began recruiting participants in October 1993, is funded by the National
Cancer Institute (NCI), the U.S. Government's principal agency for cancer
research.
2. What are clinical trials and clinical chemoprevention trials?
Clinical trials are research studies conducted with people. There are many
types of clinical trials. They range from studies to prevent, detect,
diagnose, and treat a disease to studies of the psychological impact of the
disease and ways to improve a participant's comfort and quality of life.
Chemoprevention trials, one type of clinical trial, look at possible ways to
prevent cancer using drugs, vitamins, or other agents. The PCPT is the
largest chemoprevention trial ever done with men. (The Breast Cancer
Prevention Trial, designed to find out if the drug tamoxifen could prevent
breast cancer in women at increased risk for the disease, is another
large-scale chemoprevention trial sponsored by NCI. The results of the BCPT,
reported in September 1998, showed 49 percent fewer diagnoses of invasive
breast cancer in women who took tamoxifen versus those that took a placebo [an
inactive substance that looks the same as, and is administered in the same way
as, a drug in a clinical trial]. Also, women on tamoxifen had 50 percent
fewer noninvasive breast tumors, such as ductal or lobular carcinoma in situ.)
3. Who is coordinating the PCPT? How long will the trial last?
Researchers with the Southwest Oncology Group (SWOG), based in San Antonio,
Texas, are coordinating the study, which is being conducted at 222 sites
across the United States. SWOG is a cooperative group of cancer researchers
from medical centers around the country. Cooperative groups work with NCI in
developing new ways to prevent and treat cancer.
Researchers from two other cooperative groups, the Eastern Cooperative
Oncology Group (ECOG) and the Cancer and Leukemia Group B (CALGB), are also
participating in the PCPT. The trial is planned to last a total of 10 years.
The recruitment for the trial lasted about three years, and each man will
participate for seven years.
4. Who is participating in the PCPT?
Men 55 years of age and older who are in good health and show no evidence of
prostate cancer have been recruited to participate in the study (see questions
6-8).
5. Why are only men 55 years of age and older participating in the PCPT?
Many diseases, including prostate cancer, occur more frequently in older
persons. The risk of developing prostate cancer increases with age, and about
98 percent of prostate cancer cases occur in men ages 55 and older. Thus, the
PCPT's age requirement was set to ensure that men who are at risk for the
disease were targeted.
6. What tests were used to determine eligibility for the PCPT?
Men who were recruited to participate in the PCPT had a digital rectal exam
(DRE) and a blood test for prostate-specific antigen (PSA). These tests are
commonly used to help detect prostate cancer. To participate, a man must have
had a DRE that showed no sign of prostate cancer, and a PSA blood level of 3.0
ng/ml or less. A PSA of 4.0 ng/ml or less is considered normal, but a cutoff
level of 3.0 was chosen for the PCPT to reduce the chance that a man may have
entered the trial with early, undiagnosed prostate cancer.
7. Are men with benign prostate enlargement included in the trial?
Men who have an enlarged prostate — a common condition in older men — were
only included in the trial if the condition was not severe enough to require
immediate treatment. Benign prostate enlargement often causes urinary
obstruction, and may be treated with an operation called transurethral
resection of the prostate (TURP) or with finasteride or other drugs.
8. What other factors were considered when enrolling men into the PCPT?
Men who have been diagnosed with any cancer, other than basal cell or squamous
cell cancers of the skin were not included in the trial unless they had been
free of cancer for at least five years. Men who had hormonal therapy (including
finasteride or anabolic steroids) or who had chemotherapy or radiation therapy
for any cancer, did not meet the eligibility criteria for inclusion into the
trial. In addition, men who have had urinary retention problems or who were
receiving anticoagulant (blood-thinning) medication — excluding aspirin —
were not included in the trial.
9. Will every man in the trial receive finasteride?
The 18,000 men in the PCPT will be randomized (selected by chance) to receive
either finasteride or a placebo (an inactive pill that looks like
finasteride). In a process known as "double-blinding", neither the participant
nor his physician will know which pill he is receiving. One-half of the men
in the trial will get finasteride, and one-half will get a placebo. Setting
up a trial in this way allows researchers to clearly see what the true
benefits and side effects of finasteride may be without the influence of other
factors such as the expectations of participants or researchers.
10. What is the dose of finasteride and how long will it be given?
All men in the trial will take one pill per day for up to seven years, either a
5-milligram dose of finasteride or a placebo.
11. How much will the finasteride cost?
Participants do not pay for the finasteride or the placebo. The company that
manufactures finasteride, Merck and Co., Inc., of Whitehouse Station, New
Jersey, is providing both the finasteride and the placebo without charge.
12. Are men required to have any medical exams?
A blood cholesterol test will be done at the time of the first visit to the
study site. Participants are required to have annual DREs and PSA blood tests
for the duration of the study. If any problem is discovered through a DRE or
PSA screening during the course of the study, a prostate biopsy will be done
at that time to check for prostate cancer. At the end of the seven years in the
trial, each participant will have a biopsy done. A prostate biopsy involves
removing a small sample of prostate tissue with a needle placed into the
prostate gland and examining the sample under a microscope for evidence of
cancer.
13. Who will pay for these medical exams?
Annual analysis of blood samples for PSA and the biopsy at the end of seven years
will be provided without charge. A cholesterol screening test will be
provided free of charge to all study participants at the first visit to the
study site. The only charges to participants will be for routine health care
that all men in this age group should have.
Physician, medical examination, and general clinic costs, including DREs and
drawing blood for PSA testing, will be charged to the participant in the same
way as if he were not part of the trial. However, the costs for these tests
may be covered by a participant's health insurance. If cancer or other
prostate problems are discovered during the regular exams, the participant
will be referred to his personal physician for appropriate care. Costs for
diagnosis and treatment of prostate problems, prostate cancer, or other
medical conditions during the seven years of the study are also the responsibility
of the participant.
14. What are the responsibilities of men participating in this trial?
Men in the PCPT need to be committed to participating in the trial for at
least seven years. They also have to take a pill each day for seven years, and will
have to visit the study center every six months to pick up a new supply of
pills. Men must also have follow-up examinations (DRE, PSA, and physical exam)
once a year. At the time of these exams, they will also be required to
complete some forms and questionnaires. Participants must also report any
side effects they experience. Every effort will be made to make follow-up
appointments convenient and to ensure that all men who participate in the
trial feel comfortable with their involvement. Although participants may
withdraw at any time for any reason, the trial's success will depend on the
continued participation of men who enroll.
Finasteride
15. What is finasteride?
Finasteride is a drug, taken by mouth as a pill, that is used to treat
patients with symptomatic noncancerous enlargement of the prostate, also known
as benign prostatic hyperplasia (BPH). The U.S. Food and Drug Administration
(FDA) approved the drug for this use in 1992. Finasteride has been prescribed
to about 500,000 men in 25 countries. However, it has never before been used
in an attempt to prevent cancer.
16. How does finasteride work in treating benign prostate enlargement?
Finasteride reduces levels of dihydrotestosterone (DHT), a male hormone that
is important in normal and abnormal prostate growth. DHT plays a key role in
benign prostate enlargement and is also believed to be involved in the
development of prostate cancer.
Finasteride works by blocking the action of an enzyme, 5-alpha reductase, that
is needed to convert the hormone testosterone into DHT. Because the chemical
structure of finasteride resembles that of testosterone, it binds to 5-alpha
reductase, making the enzyme unavailable for the conversion of testosterone to
DHT — a process known as competitive inhibition.
17. Why is finasteride now being tested to prevent prostate cancer?
The development of prostate cancer is strongly influenced by male hormones.
DHT in particular is known to be important for the growth of prostate cells.
Because finasteride reduces levels of DHT, researchers believe the drug may
prevent the cellular changes that can lead to prostate cancer. In support of
this hypothesis, finasteride has been shown to inhibit the growth of prostate
cancer cells in tissue culture ("test tube") experiments. Studies have shown
that men with inherited 5-alpha reductase deficiency have not developed
prostate cancer. Also, studies comparing different population groups suggest
that men who have lower levels of 5-alpha reductase have lower rates of
prostate cancer than other men.
18. Can finasteride cause side effects?
Like most medications, whether over-the-counter preparations, prescription
drugs, or drugs in clinical trials, finasteride may cause side effects.
Finasteride primarily affects the prostate, and its side effects appear to be
rare and relatively mild — an important consideration when testing a drug in
healthy people.
In the manufacturer's clinical trials, carried out to gain FDA approval to
market finasteride, approximately 1,100 men with benign prostate enlargement
were given either finasteride or a placebo. Side effects were rare and were
observed in a small number of men in both groups. Decreased sexual desire was
reported by 3.3 percent of men given finasteride, compared with 1.6 percent of
men given a placebo; impotence (difficulty achieving an erection) was reported
by 3.7 percent of the finasteride group, compared with 1.1 percent of the
placebo group; and decreased ejaculatory volume was reported by 2.8 percent of
the finasteride group, compared with 0.9 percent of the placebo group.
However, a recent study suggests that these problems frequently diminish over
time in men who continue to take the drug.
It is unknown how much finasteride can be absorbed by a woman's body through
semen, or whether finasteride could harm a developing male fetus. Because of
these uncertainties, a man whose sexual partner could become pregnant should
discuss this issue thoroughly with the study physician.
Because finasteride is a relatively new drug, the possibility remains that
other side effects will be identified after more men have taken it for longer
periods of time. Participants in the PCPT will be asked twice a year about
side effects and will be encouraged to call the study site any time they have
symptoms or concerns they feel may be related to the trial.
Other Questions
19. What is the prostate gland?
The prostate is a male sex gland. It produces a thick fluid that forms part
of semen, enabling sperm to be released during ejaculation. The normal
prostate is about the size of a walnut, and is located below the bladder and
in front of the rectum. The prostate surrounds the upper part of the urethra,
the tube that empties urine from the bladder.
20. How common is prostate cancer?
Prostate cancer is the most frequently diagnosed cancer among American men,
other than skin cancer. In 1999, about 179,300 men will be diagnosed with
prostate cancer in the United States, and about 37,000 men will die of the
disease.
21. Who is at risk of developing or dying of prostate cancer?
Age is the most significant risk factor for prostate cancer. The disease is
rare in men under age 45, but incidence rates rise rapidly with age. Annual
U.S. incidence rates from 1992 to 1996 were 49.6 cases per 100,000 men under
age 65, and 1,131.9 cases per 100,000 men ages 65 and older. Most men who get
prostate cancer are in their seventies or older.
Men with a family history of prostate cancer are at increased risk for the
disease. Black men have significantly higher incidence rates than white men,
though incidence among white men is rising faster, probably as a result of
intensified screening. Mortality rates among black men are twice as high as
those of white men. This is probably due in part to the fact that black men,
on average, are diagnosed at later stages of disease than white men.
22. Why is the PCPT so important?
Prostate cancer is an important public health problem. Although the number of
men being diagnosed with prostate cancer has decreased slightly in the past
few years, 1996 incidence rates (the latest available) are nearly double the
incidence rates from 20 years earlier. The decline in heart disease mortality
in recent decades means that more men are living to older ages at which risk
for prostate cancer is highest. Because the causes of the disease are largely
unknown, risk factors are difficult to identify.
The hormone dependence of prostate growth offers one possible avenue of
intervention before cancer has a chance to develop. Finasteride works in
treating benign prostate enlargement by altering the hormonal balance in the
prostate. The PCPT will test whether finasteride may prevent prostate cancer
through the same hormonal mechanism. A large, controlled clinical trial is
the only way to determine whether the benefits outweigh any risk, and whether
finasteride should be approved for general use as a preventive agent. The
drug's relatively mild side effects make it a good candidate for testing in
healthy people.
The researchers will also use reports of participants to assess the effects of
finasteride on men's sexual and urinary functioning and other quality-of-life
measures. In addition, the trial will give researchers an opportunity to
observe the effect of finasteride on PSA levels of men taking the drug, and to
study the usefulness of DRE and PSA as screening tests for prostate cancer.
23. How will healthy men benefit from participating in the PCPT?
Although finasteride's effectiveness is currently unknown, researchers hope
that the drug will prevent prostate cancer from occurring in men receiving it
in the trial. All participants will receive regular exams, which can help
detect prostate cancer in earlier stages. Some men wanted to participate
because they are at increased risk for the disease. Men receiving finasteride
may experience shrinkage of existing prostate enlargement, although this is
not a direct aim of the study. In addition, men may find satisfaction in
contributing to medical science and perhaps helping other men who may benefit
from the results of the trial in the future.
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