It's been a roller coaster for
tamoxifen lately. The grand old dame of breast cancer
drugs cleared her name of increased stroke risk only to
find that younger, sexier drugs are hard on her heels.
Aromatase inhibitors have not only outperformed tamoxifen
in a number of head-to-head trials, but did so with fewer
side effects. The final slap in the face may be this month's
endorsement of aromatase inhibitors by the American Society
of Clinical Oncology (ASCO). The new breast cancer guidelines
by ASCO, published online December 8 in the Journal
of Clinical Oncology, suggest that estrogen receptor-positive
or receptor-unknown postmenopausal women should consider
switching from tamoxifen to an aromatase inhibitor such
as anastrozole or exemestane, which reduces estrogen levels.
The recommendations aren't surprising
in view of studies like that published in the December
11 issue of The Lancet. This research found a
13% improvement in disease-free survival, a 14% reduction
in distant metastases, and a whopping 42% reduction
in contralateral tumours among patients using anastrozole
as compared to tamoxifen. The study, which followed
9,366 patients for a median of 33 months, also found
a significantly lower incidence of endometrial cancer,
vaginal bleeding, cerebrovascular events, venous thromboembolic
events and hot flushes with anastrozole, but a higher
incidence of fractures and arthralgia.
IN
THE PIPELINE
Pfizer, the maker of exemestane tablets, has submitted
an FDA application to have the drug approved as a firstline
treatment for hormone-receptive breast cancer in postmenopausal
patients — the role currently occupied by tamoxifen.
For now, exemestane is approved in Canada but it's only
indicated for patients whose cancer has progressed despite
tamoxifen treatment.
"The adjuvant approval of exemestane
would provide oncologists with a treatment regimen that
significantly reduces the recurrence of breast cancer,"
said Dr Stephen Jones, medical director at US Oncology
Research. "This filing is an important step toward providing
postmenopausal women with a critical treatment option
that can significantly improve survival of early breast
cancer when compared to tamoxifen."
Despite the encouraging study news,
aromatase inhibitors haven't been around long enough
to be sure of their long-term effects. In fact, the
only five-year survival rates available come from patients
who took two to three years of tamoxifen followed by
two to three years of an aromatase inhibitor. Without
longer-term data, it's impossible to predict the price
that will be paid in terms of osteoporosis and other
problems associated with low estrogen levels. But these
concerns may weigh little enough when set against the
patient's overriding prerogative to banish their tumour.
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