Fulvestrant: New Treatment Option for Advanced Breast Cancer
Key Words: breast cancer,
fulvestrant,
postmenopausal women. (Definitions of many
terms related to cancer can be found in the
Cancer.gov Dictionary.)
A new drug called fulvestrant (Faslodex®) was as effective as another drug,
anastrozole (Arimidex®), in postmenopausal women with advanced, previously treated breast cancer, according to two studies published in the August 15, 2002, issue of the Journal of Clinical Oncology.
The women in the studies had been previously treated with the drug
tamoxifen, only to have their breast cancer
return. Anastrozole belongs to a class of drugs called
aromatase inhibitors (AIs). Drugs from this class are the current
standard therapy for breast cancer that has
recurred or progressed after treatment with tamoxifen.
The new fulvestrant results "mean that patients with advanced breast cancer
and their doctors now have an additional treatment option," said Jeff
Abrams, M.D., of the National Cancer Institute's Cancer Therapy Evaluation
Program.
The first of the two studies, led by C.K. Osborne, M.D., of Baylor College of Medicine in Houston, Texas, involved 400 patients in the United States and Canada who were
randomly assigned to receive either
fulvestrant or anastrozole (see
the journal abstract). Fulvestrant is given as a monthly injection,
anastrozole as a daily pill, so the researchers included in their study two
placebos, or dummy treatments. Patients who received the fulvestrant injection
also received a dummy pill; those who were given the anastrozole pill were also
injected with a dummy substance. Neither patients or their doctors knew which
was the active treatment. This kind of "double-blind" approach helps
to prevent the kind of bias that can weaken study results.
After an average of 17 months of follow-up, fulvestrant delayed disease
progression by 5.4 months on average, compared with 3.4 months for anastrozole.
This difference, however, was not statistically significant (that is, it could
have occurred by chance). In patients who responded to treatment, the average
duration of response was 19 months for those treated with fulvestrant and 11
months for those who received anastrozole. The number of patients experiencing
adverse effects of treatment, as well as the severity of those adverse effects,
were similar in both groups.
In the second study, led by A. Howell, M.D., of Christie Hospital National Health Service Trust in Manchester, United Kingdom, 451 patients in Europe, South Africa, and Australia were randomly assigned to receive either fulvestrant by monthly injection or anastrozole in a daily pill (see
the journal abstract). Unlike the U.S.-Canadian study, this study was not designed in a double-blinded fashion. Thus, both patients and their doctors knew who was receiving which treatment.
The results of this study were very similar to those of the U.S.-Canadian study.
Response rates and delays in disease progression were about the same in both
groups of patients.
(Note: After an extended follow-up, combined data from the two studies were subseqently published in the July 15, 2005, issue of the journal Cancer. These results showed that "fulvestrant was similar to anastrozole with respect to overall survival in the second-line treatment of postmenopausal women" with advanced breast cancer. See the journal abstract.)
Now that fulvestrant appears to be as effective as anastrozole, doctors and
patients should consider several factors, including the patient's prior
treatment and each drug's side effects, when making treatment decisions, said
Abrams.
"If a patient gets tamoxifen as first-line therapy," said Abrams,
"then either fulvestrant or an AI is a reasonable second-line choice.
However, some patients are getting AIs first-line now, so the actual choice for
some may be between fulvestrant and tamoxifen."
Fulvestrant has been shown to work in patients whose tumors progressed after
treatment with tamoxifen. But it's not yet known whether the opposite is true
-- that is, whether tamoxifen helps patients whose tumors have recurred after
treatment with fulvestrant. For this reason, said Abrams, "it would be
reasonable to use tamoxifen or an AI first and save fulvestrant for second-line
therapy."
Tamoxifen, AIs, and fulvestrant are effective only in patients whose tumors are
sensitive to the hormones
estrogen and
progesterone. The drugs work in different
ways to prevent these hormones from stimulating breast cancer growth.
Tamoxifen attaches to the estrogen receptor in the tumor, which blocks
estrogen's effect on the cancer cells in breast tissue but may mimic the effect
of estrogen elsewhere, such as the uterus or bone. AIs, by contrast, reduce
overall estrogen levels by inhibiting the body's production of the hormone.
Fulvestrant, like tamoxifen, attaches to the estrogen receptor but, unlike
tamoxifen, it destroys the receptor, thereby blocking all estrogen activity.
Because of their different mechanisms of action, the drugs have different side
effects, explained Abrams. "Tamoxifen has protective effects against
osteoporosis because it stimulates the
estrogen receptor in bone. AIs and fulvestrant do not seem to have this
protective effect on bone, whereas tamoxifen, by stimulating the estrogen
receptor in the uterus, increases the risk of
endometrial cancer. AIs and fulvestrant are
unlikely to have this effect on the uterus."
Finally, tamoxifen is effective in premenopausal women with breast cancer
whereas AIs are not, said Abrams. Clinical studies have not yet shown whether
fulvestrant is effective in premenopausal women.
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