Biomedical Engineering Reference
In-Depth Information
with superior response rates, TTP, and overall survival compared
with first-line tamoxifen.
66
), as
mentioned earlier, competes with estrogen for the ER, effectively
blocks ER dimerization and DNA binding, increases ER turnover,
and inhibits nuclear uptake of the receptor.
The
pure
anti-estrogen
drug,
fulvestrant
(Faslodex
®
33,34
It is approved for
postmenopausal patients with disease progression following anti-
estrogen therapy. Fulvestrant is an active agent in patients who are
refractory to tamoxifen or an AI.
67-69
Fulvastrant given at 500 mg
every 14 days for the first month followed by every 28 days thereafter,
significantly increased progression-free survival compared with 250
mg every 28 days.
70
When fulvestrant was compared with tamoxifen
as the first-line treatment for metastatic disease, no differences in
response rates, TTP and treatment tolerability were observed.
71
One advantage of fulvestrant is the monthly intramuscular injection
instead of daily intake.
In general, multiple lines of endocrine therapies can be used for
patients with ER+/PgR+ advanced disease before the initiation of
systemic chemotherapy. The objective response rates of the first line
therapy are higher (21 to 33%, 33%, 32%, and 46% for tamoxifen,
anastrozole, letrozole and exemestane, respectively) than those of
the second line treatment (10.3-12%, 19%, and 23% for anastrozole,
letrozole and exemestane, respectively).
A meta-analysis
of 37 trials, including 11,403 women with advanced breast cancer,
showed a significant survival benefit for treatment with an AI over
other endocrine therapies.
64,66,72-76
63
The selection of treatment choices also takes into consideration
of the toxicity profiles (Table 5.1), tumor burden/location, and
history of response to hormonal treatment. Considerations are also
given for a third or fourth-line endocrine therapy using progestins,
androgens or estrogens for selected patients. The various endocrine
therapies differ somewhat in terms of efficacy and substantially
vary with regard to tolerability. Because the toxicities of endocrine
therapy are usually tolerable, some physicians would prefer exhaust
all endocrine treatment options before considering chemotherapy.
Based on the current clinical data, AIs are recommended as the
treatment of choice if a patient has relapsed while receiving adjuvant
tamoxifen or has not received any adjuvant endocrine treatment
or has relapsed more than 1 year after discontinuing adjuvant
tamoxifen or an AI. If a patient has relapsed during or within 12
