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Frequently Asked Questions |
Frequently Asked Questions About
the Study of Tamoxifen and
Raloxifene (STAR)
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 people) 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. Findings from the BCPT were reported in the September 16, 1998,
issue of the Journal of the National Cancer Institute.
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. One of these studies was the Multiple Outcomes of
Raloxifene Evaluation (MORE) trial. The MORE Trial was designed to study
the effects of raloxifene on osteoporosis in postmenopausal women.
Researchers also tracked rates of breast cancer and observed a reduction
in the risk of breast cancer among women who took raloxifene. The results
of this study were reported in the June 16, 1999, issue of the Journal of
the American Medical Association.
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.
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.
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, as long as any
treatment for the condition was limited to local excision. Mastectomy,
radiation, or systemic therapy would disqualify a woman with LCIS from the
study.
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.
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 cancer
(except basal or squamous cell skin cancer), 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.
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.
10. Does tamoxifen cause cancers of the uterus?
Tamoxifen
increases the risk of two types of cancer that can develop in the uterus:
endometrial cancer, which arises in the lining of the uterus, and uterine
sarcoma, which arises in the muscular wall of the uterus. Like all
cancers, endometrial cancer and uterine sarcoma are potentially life
threatening. Women who have had a hysterectomy (surgery to remove the
uterus) and are taking tamoxifen are not at increased risk for these
cancers.
In the BCPT, women who took tamoxifen had more than twice the chance
of developing endometrial cancer compared with women who took a placebo
(an inactive substance that looks the same as, and is administered in
the same way as, tamoxifen). The risk of endometrial cancer in women
taking tamoxifen was in the same range as (or less than) the risk in
postmenopausal women taking single-agent estrogen replacement therapy.
This risk is about 2 cases of endometrial cancer per 1,000 women taking
tamoxifen each year.
Most of the endometrial cancers that have occurred in women taking
tamoxifen have been found in the early stages, and treatment has usually
been effective. However, for some breast cancer patients who developed
endometrial cancer while taking tamoxifen, the disease was life
threatening.
Information collected by the U.S. Food and Drug Administration
indicates that women who have used tamoxifen for breast cancer treatment
or prevention have an increased risk of developing uterine sarcoma.
Review of all the NSABP clinical trials using tamoxifen confirmed an
increased risk of this rare cancer. In the BCPT, there are about 2 cases
per 10,000 women taking tamoxifen each year. Research to date indicates
that uterine sarcomas are more likely to be diagnosed at later stages
than endometrial cancers, and may therefore be harder to control and
more life-threatening than endometrial cancer.
Abnormal vaginal bleeding and lower abdominal (pelvic) pain are
symptoms of cancers of the uterus. Women who are taking tamoxifen should
talk with their doctor about having regular pelvic examinations, and
should be checked promptly if they have any abnormal vaginal bleeding or
pelvic pain between scheduled exams.
11. Does tamoxifen cause other serious side effects?
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).
12. 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.
13. 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.
14. 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, AstraZenecain
Wilmington,Delaware, and the maker of raloxifene, Eli Lilly and Company in
Indianapolis, Indiana, are providing the active pills and the look-alike
placebos without charge.
15. 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.
16. How can a woman enroll in the trial?
Postmenopausal women
who are interested in participating in STAR should contact
Decatur Memorial Hospital
Women's Health, Education & Research
2300 North Edward Street
Decatur, Illinois 62526
217-876-2381
Email: teresal@dmhhs.org
or 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 or NCI's
clinical trials Web site.
17. 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 STAR. 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, AstraZeneca, and Eli Lilly and Company
with annual reports on STAR that summarize the overall data collected to
date (only the DSMC receives unblinded data).
18. 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
clinical trials 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.
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