Questions and Answers:
The Study of Tamoxifen and Raloxifene (STAR)
1.
What is the Study of Tamoxifen and Raloxifene (STAR)?
2.
What is tamoxifen?
3.
What is raloxifene?
4.
Who is eligible to participate in STAR?
5.
Why can't premenopausal women participate in STAR?
6.
What factors are used to determine increased risk of breast cancer
for the participants?
7.
How will a potential participant's risk of breast cancer be determined?
8. What other factors affect
eligibility for the study?
9.
What are the common side effects of tamoxifen and raloxifene?
10.
Does tamoxifen have any serious side effects?
11.
Does raloxifene have any serious side effects?
12.
Who will get which drug?
13.
Why does everyone have to take two pills?
14.
Are participants required to have any medical exams? Who will
pay for these exams?
15.
How can a woman enroll in the trial?
16.
How is the safety of participants ensured? Is the trial monitored?
17.
What is the National Surgical Adjuvant Breast and Bowel Project?
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1. What is the Study
of Tamoxifen and Raloxifene (STAR)?
The Study of Tamoxifen and Raloxifene (STAR) is a clinical trial
(a research study conducted with volunteers) designed to see how
the drug raloxifene (Evista®) compares with the drug tamoxifen
(Nolvadex®) in reducing the incidence of breast cancer in women
who are at an increased risk of developing the disease. Researchers
with the National Surgical Adjuvant Breast and Bowel Project (NSABP)
are conducting the study at more than 400 centers across the United
States, Puerto Rico, and Canada. The study is primarily funded
by the National Cancer Institute (NCI), the U.S. government’s
main agency for cancer research.
2. What is tamoxifen?
Tamoxifen is a drug, taken by mouth as a pill. It has been used
for more than 20 years to treat patients with breast cancer. Tamoxifen
works against breast cancer, in part, by interfering with the
activity of estrogen, a female hormone that promotes the growth
of breast cancer cells. In October 1998, the U.S. Food and Drug
Administration (FDA) approved tamoxifen to reduce the incidence
of breast cancer in women at high risk of the disease based on
the results of the Breast Cancer Prevention Trial (BCPT). The
BCPT is a study of more than 13,000 pre- and postmenopausal high-risk
women ages 35 and older who took either tamoxifen or a placebo
(an inactive pill that looked like tamoxifen) for up to five years.
NSABP conducted the BCPT, which also showed that tamoxifen works
like estrogen to preserve bone strength, decreasing fractures
of the hip, wrist, and spine in the women who took the drug.
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3. What is raloxifene?
Raloxifene is a drug, taken by mouth as a pill. In December 1997,
it was approved by the FDA for the prevention of osteoporosis
in postmenopausal women. Raloxifene is being studied because large
studies testing its effectiveness against osteoporosis have shown
that women taking the drug developed fewer breast cancers than
women taking a placebo.
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4.
Who is eligible to participate in STAR?
Women at increased risk for developing breast cancer, who have
gone through menopause and are at least 35 years old, can participate
in STAR. All women must have an increased risk of breast cancer
equivalent to or greater than that of an average 60- to 64-year-old
woman. At that age, about 17 of every 1,000 women are expected
to develop breast cancer within five years.
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5. Why can't premenopausal
women participate in STAR?
STAR is limited to postmenopausal women because the drug raloxifene
has yet to be adequately tested for long-term safety in premenopausal
women. NCI recently launched a separate study to evaluate the
safety of raloxifene in premenopausal woman.
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6. What factors are used
to determine increased risk of breast cancer for the participants?
Increased risk of breast cancer is determined in one of two ways.
The risk for most women is determined by a computer calculation
based on the following factors:
- Current
age;
- Number
of first-degree relatives (mother, daughters, or sisters) diagnosed
with breast cancer;
- Whether
a woman had any children and her age at her first delivery;
- The
number of breast biopsies a woman has had, especially if the
tissue showed a condition known as atypical hyperplasia; and
- The
woman's age at her first menstrual period.
Women
diagnosed as having lobular carcinoma in situ (LCIS), a condition
that is not cancer but indicates an increased chance of developing
invasive breast cancer, are eligible based on that diagnosis alone.
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7. How will a potential
participant's risk of breast cancer be determined?
Each potential participant will complete a one-page questionnaire
(risk assessment form) which will be forwarded to NSABP by the
local STAR clinical staff. The NSABP will use computer software
to generate an individualized risk profile based on the information
provided and will return the profile to the local STAR site so
that it can be given to the potential participant. The profile
will estimate the woman's chance of developing breast cancer over
the next five years and will also present the potential risks
and benefits of the study drugs. The woman can then use this information
to help her decide whether or not she is interested in participating
in STAR.
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8. What other factors
affect eligibility for the study?
Certain existing health conditions affect eligibility for the
study. Health professionals at the STAR site will discuss these
with each potential participant. For example, women with a history
of blood clots, stroke, or certain types of heartbeat irregularities
cannot participate. Women whose high blood pressure or diabetes
is not controlled also cannot participate.
Also, women taking hormone replacement therapy (estrogen or an
estrogen/progesterone combination) cannot take part in the trial
unless they stop taking this medication. Those who stop taking
these hormones are eligible for the study three months after they
discontinue the drugs. Women who have taken tamoxifen or raloxifene
for no more than three months are eligible for the study, but
they must also stop the medication for three months before joining
STAR.
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9. What are the common
side effects of tamoxifen and raloxifene?
Like most medications, including over-the-counter medications,
prescription drugs, or drugs in research studies, tamoxifen and
raloxifene cause adverse effects in some women. The effects experienced
most often by women taking either drug are hot flashes and vaginal
symptoms, including discharge, dryness, or itching. It is possible
that some women may experience leg cramps, constipation, pain
with intercourse, sinus irritation or infection, or problems controlling
the bladder upon exertion. Treatments that may minimize or eliminate
most of these side effects will be available to the participants.
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10. Does tamoxifen have
any serious side effects?
The best information available about the serious side effects
of tamoxifen comes from 30 years of clinical trials, including
the BCPT. In the BCPT, women taking tamoxifen had more than twice
the chance of developing endometrial cancer (cancer of the lining
of the uterus or womb) compared with women who took the placebo
(36 of the 6,600 women taking tamoxifen vs. 15 of the 6,600 women
taking placebo). The risk was higher in women over the age of
50. The increased risk is in the same range as the risk for postmenopausal
women taking single-agent estrogen replacement therapy. Like all
cancers, endometrial cancer is potentially life-threatening. Women
who have had a hysterectomy (surgery to remove the uterus) are
not at risk for endometrial cancer.
Women taking tamoxifen in the BCPT had three times the chance
of developing a pulmonary embolism (blood clot in the lung) as
women who took the placebo (18 women taking tamoxifen vs. six
on placebo). Three women taking tamoxifen died from these embolisms.
Women in the tamoxifen group were also more likely to have a deep
vein thrombosis (a blood clot in a major vein) than women on placebo
(35 women on tamoxifen vs. 22 on placebo). Women taking tamoxifen
also appeared to have an increased chance of stroke (38 women
on tamoxifen vs. 24 on placebo).
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11. Does raloxifene
have any serious side effects?
Information about raloxifene is limited compared to the data available
on tamoxifen because of the shorter time it has been studied (about
five years) and the smaller number of women who have been studied.
Studies of raloxifene have generally involved women who received
the drug to determine its effect on osteoporosis, and the duration
of both therapy and follow-up have been short. Women taking raloxifene
in clinical trials have about three times the chance of developing
a deep vein thrombosis or pulmonary embolism as women on a placebo.
In osteoporosis studies of raloxifene, the drug did not increase
the risk of endometrial cancer. An important part of STAR will
be to assess the long-term safety of raloxifene vs. tamoxifen
in women at increased risk of breast cancer.
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12. Who will get which
drug?
Participants in STAR will be randomized (assigned by chance) to
receive either tamoxifen or raloxifene. In a process known as
"double blinding", neither the participant nor her physician
will know which pill she is receiving. Setting up a study in this
way allows the researchers to directly compare the true benefits
and side effects of each drug without the influence of other factors.
All women in the study will take two pills a day for five years:
half will take active tamoxifen and a raloxifene placebo (inactive
pill that looks like raloxifene); the other half will take active
raloxifene and a tamoxifen placebo (inactive pill that looks like
tamoxifen). All women will receive one of the active drugs; no
one in STAR will receive only the placebo. The dosages are 20
mg of tamoxifen and 60 mg raloxifene.
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13. Why does everyone
have to take two pills?
Tamoxifen and raloxifene have different shapes. The trial would
not be double blinded if participants or physicians could tell
which drug they were receiving because of its shape. The maker
of tamoxifen, Zeneca Pharmaceuticals, Wilmington, Del., and the
maker of raloxifene, Eli Lilly and Company, Indianapolis, Ind.,
are providing the active pills and the look-alike placebos without
charge.
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14. Are participants
required to have any medical exams? Who will pay for these exams?
Participants are required to have blood tests, a mammogram, a
breast exam, and a gynecologic exam before they are accepted into
the study. These tests will be repeated at intervals during the
trial. Physicians' fees and the costs of medical tests will be
charged to the participant in the same fashion as if she were
not part of the trial; however, the costs for these tests generally
are covered by insurance. Every effort is made to contain the
costs specifically associated with participation in this trial,
and financial assistance is available for some women.
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15. How can a woman
enroll in the trial?
Postmenopausal women who are interested in participating in STAR
should contact the center nearest to them. To locate the nearest
center in the United States (including Puerto Rico) by phone,
a woman can call the NCI's Cancer Information Service at 1-800-4-CANCER
(1-800-422-6237). The number for callers with TTY equipment is
1-800-332-8615.
In Canada, participating centers can be located by calling the
Canadian Cancer Society's Cancer Information Service at 1-888-939-3333.
To locate the nearest STAR center via Internet, visit NSABP's
Web site at http://www.nsabp.pitt.edu
or NCI's clinical trials STAR home page at http://cancertrials.nci.nih.gov/NCI_CANCER_TRIALS/zones/TrialInfo/News/star/.
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16. How is the safety
of participants ensured? Is the trial monitored?
The safety of participants is of primary importance to STAR investigators.
There are strict requirements about who can join the trial as
well as frequent monitoring of participants' health status. An
independent Data Safety and Monitoring Committee (DSMC) will provide
oversight of the trial. The DSMC includes medical and cancer specialists,
biostatisticians, and bioethicists who have no other connection
to NSABP. The DSMC will meet semiannually and review unblinded
data from all participants. Two other committees will also provide
oversight. The Participant Advisory Board (PAB) is made up of
16 women from the BCPT. As women join STAR, board membership will
change to include STAR participants. The PAB meets semiannually
with professionals from NSABP and NCI and provides feedback on
many study-related functions such as informed consent, participant
recruitment, and communications issues. The STAR Steering Committee
is made up of NSABP investigators, breast cancer advocates, experts
from other medical disciplines, as well as NCI and NSABP personnel.
The committee, which also meets semiannually, is charged with
providing overall administrative oversight of the trial.
In addition, NSABP provides the U.S. FDA, NCI, Zeneca Pharmaceuticals,
and Eli Lilly and Company with annual reports on STAR that summarize
the overall data collected to date (only the DSMC receives unblinded
data).
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17. What is the National
Surgical Adjuvant Breast and Bowel Project?
The NSABP is a cooperative group with a 40-year history of designing
and conducting clinical trials, the results of which have changed
the way breast cancer is treated, and now, prevented. Results
of research studies conducted by NSABP researchers have been the
dominant force in altering the standard surgical treatment of
breast cancer from radical mastectomy to lumpectomy plus radiation.
This group was also the first to demonstrate that adjuvant therapy
could alter the natural history of breast cancer, thus increasing
survival rates.
Source: from the National Cancer Institute & the National
Institutes of Health
Reference:
from the National Institute on Deafness and Other Communication
Disorders (NIDCD), one of the National Institutes of Health
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