WASHINGTONEnrollment for the Study of Tamoxifen and Raloxifene
(STAR), the largest cancer prevention trial yet undertaken, began May
25, and randomization of participants to the trials two arms is
expected to start in July. The double-blind study of 22,000 woman at
increased risk of breast cancer will compare the two drugs
effectiveness in preventing the disease as well as their side-effects profiles.
Basically, the principal question that is being asked is
whether raloxifene is superior to tamoxifen in reducing the incidence
of breast cancer and whether it can do so with fewer adverse
effects, said Norman Wolmark, MD, chairman of the
National Surgical Adjuvant Breast and Bowel Project (NSABP).
NSABP will conduct STAR for the National Cancer Institute at more
than 400 centers in the United States, Canada, and Puerto Rico. Women
in the tamoxifen arm will receive 20 mg/day and the raloxifene group
will get 60 mg/day for 5 years. Each woman will get two pills to take
daily, one her active drug and the second a placebo that looks like
the other drug used in the trial.
Both tamoxifen (Nolvadex) and raloxifene (Evista) are selective
estrogen-receptor modulators (SERMs). Tamoxifen has been used for
more than 2 decades to treat breast cancer patients. Last year,
results from the 13,000-woman Breast Cancer Prevention Trial (BCPT)
showed that high-risk women taking tamoxifen for 5 years had a 49%
lower incidence of the disease than women taking placebo.
Last October, the Food and Drug Administration approved the use of
tamoxifen to reduce breast cancer incidence in high-risk women.
However, tamoxifen users in the BCPT had significantly higher
incidences of endometrial cancer, pulmonary embolism, deep vein
thrombosis, and stroke.
The FDA approved raloxifene in December 1997 for the prevention of
osteoporosis in postmenopausal women. Clinical trials have indicated
that the drug may also reduce the risk of developing breast cancer
and may not increase endometrial cancer risk. The incidences of deep
vein thrombosis and pulmonary embolism, however, are similar to those
with tamoxifen. These findings provide the rationale for STAR.
Enrollment criteria for STAR require a woman to be at least 35 years
old, postmenopausal, and have at least a cumulative 1.66% increased
risk of developing breast cancer over the next 5 years.
Premenopausal women are excluded because raloxifene has yet to
be adequately tested for long-term safety in premenopausal
women, according to NCI, which noted that it has recently begun
a separate study evaluating the drugs safety in that population.
Each potential STAR enrollee will complete a risk assessment form so
that the NSABP can determine her risk profile. The woman can then use
this information to help her decide whether to participate in STAR.
The computer calculation of risk uses a model developed at NCI that
evaluates a number of factors. These include age; number of
first-degree relatives diagnosed with breast cancer; whether a woman
has had any children and her age at first delivery; the number of
breast biopsies she has had, especially those with atypical
hyperplasia; and her age at menarche. Women diagnosed with lobular
carcinoma in situ are eligible for the study based solely on that diagnosis.
Women with a history of thrombosis, stroke, certain arrhythmias,
uncontrolled hypertension, or diabetes are excluded from STAR. Women
taking hormone replacement therapy or who have taken tamoxifen or
raloxifene for no more than 3 months are eligible for the study 3
months after they stop their medication.
After randomization, the follow-up is fairly
straightforward, said D. Lawrence Wickerham, MD, NSABP
associate chairman. They will have a breast exam twice a year,
a mammogram and gynecological examination once a year, and screening
blood work yearly.
Initially, NCI planned to enroll 8,000 women in the first year of
STAR, 5,000 in the second year, and 3,000 each in the following 3
years. Now, the Institute hopes all 22,000 participants can be
enrolled within 36 months.
When the results will be ready will be dependent on accrual
rates, but certainly within the next 10 years we would expect to have
those results, and if we can enter those 22,000 women rapidly, the
results will be apparent more rapidly, Dr. Wickerham said.
The NCI expects to spend between $75 and $100 million on the study
over the next 10 years, Leslie Ford, MD, associate director for
clinical research at the Division of Cancer Prevention, said at a
press conference. That briefing coincided with local press
conferences held in many cities where researchers are recruiting STAR
participants. In addition, Eli Lilly and Co. has given NSABP a $36
million grant to defray recruitment costs and to help local
researchers carry out the trial.