Femara (letrozole)
The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Hormone receptor positive or hormone receptor unknown locally advanced or metastatic breast cancer
General Information
Femara has been approved for the first-line treatment of
postmenopausal women with hormone receptor positive or hormone
receptor unknown locally advanced or metastatic breast cancer. The
drug is a once-a-day oral treatment originally approved in 1997 for
advanced breast cancer in postmenopausal women with disease
progression following antiestrogen therapy.
Estrogen has been shown to stimulate the growth of certain
hormone-dependent cancer cells. In postmenopausal women, estrogen
is primarily produced from the conversion of adrenal androgens to
estrogen. This conversion is catalyzed by an enzyme known as
aromatase. Femara contains 2.5 mg of letrozole, a compound that
blocks the action of aromatase and therefore inhibits the
conversion of androgens to estrogens.
Advanced breast cancer is the second leading cause of cancer
death among women in the United States. Over 120,000 American women
have advanced breast cancer, and approximately half of the 182,000
newly diagnosed cases of breast cancer each year are in an advanced
stage when detected.
Clinical Results
Among other studies, Femara was evaluated in a randomized,
double-blind, multinational phase III trial that compared Femara
2.5 mg to tamoxifen 20 mg in 907 postmenopausal women with locally
advanced (stage IIIB) disease, metastatic breast cancer, or
recurrences not amenable to treatment with surgery or radiotherapy.
Results of the trial demonstrated that Femara delayed progression
of advanced breast cancer for 9.4 months compared to 6.0 months for
tamoxifen. Significant differences were also observed between
Femara and tamoxifen in terms of objective response rate (30% vs.
20%), clinical benefit (49% vs. 38%) and time to treatment failure
(9.1 months vs. 5.7 months). Femara and tamoxifen were equally well
tolerated.
Side Effects
Reported adverse events for Femara vs. tamoxifen included (but
are not limited to) the following:
- Bone pain (20% vs. 18%)
- Hot flushes (18% vs. 15%)
- Back pain (17% vs. 17%)
- Nausea (15% vs. 16%)
- Dyspnea (abnormal breathing) (14% vs. 15%)
- Arthralgia (severe joint pain) (14% vs. 13%)
- Fatigue (11% vs. 11%)
- Coughing (11% vs. 10%)
Mechanism of Action
Letrozole is a nonsteroidal competitive inhibitor of the
aromatase enzyme system; it inhibits the conversion of androgens to
estrogens. In adult non-tumor and tumor-bearing female animals,
letrozole is as effective as ovariectomy in reducing uterine
weight, elevating serum LH, and causing the regression of
estrogen-dependent tumors. In contrast to ovariectomy, treatment
with letrozole does not lead to an increase in serum FSH. Letrozole
selectively inhibits gonadal steroidogenesis but has no significant
effect on adrenal mineralocorticoid or glucocorticoid
synthesis.
Letrozole inhibits the aromatase enzyme by competitively binding
to the heme of the cytochrome P450 subunit of the enzyme, resulting
in a reduction of estrogen biosynthesis in all tissues. Treatment
of women with letrozole significantly lowers serum estrone,
estradiol and estrone sulfate and has not been shown to
significantly affect adrenal corticosteroid synthesis, aldosterone
synthesis, or synthesis of thyroid hormones. (from Novartis Revised
Package Insert)
Additional Information
If you would like more information on this product, please visit
the Femara web
site.
Please visit
CancerNet, a service of the National Cancer
Institute, to learn more about breast cancer.