Company: Novartis
Approval Status: Approved January 2001
Treatment for: 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.
