The aromatase inhibitor letrozole(Drug information on letrozole) (Femara), at a dosage of 2.5 mg once daily, is an effective therapy for advanced breast cancer in postmenopausal women whose disease progresses following antiestrogen therapy, according to data published in the February 1998 Journal of Clinical Oncology. The study was conducted by the Letrozole International Trial Group and was sponsored by Novartis Pharmaceuticals Corporation.
In this international double-blind trial, 551 patients with advanced breast cancer were randomized to one of three treatment arms: 0.5 mg of letrozole, 2.5 mg of letrozole, or 160 mg of megestrol(Drug information on megestrol) acetate. The study showed that 2.5 mg of letrozole daily not only was effective but also was generally well tolerated by postmenopausal women who had disease progression following antiestrogen therapy (eg, tamoxifen(Drug information on tamoxifen) [Nolvadex]).
In the advanced disease setting when antiestrogen therapy fails, it is vital to have additional treatment options, said David Parkinson, md, vice president of clinical research at Novartis Pharmaceuticals.
These data demonstrate that Femara may be an effective option to help shrink tumors or slow the progression of the disease in postmenopausal women for whom antiestrogen therapy has failed.
In the study, an objective (complete or partial) response to treatment was demonstrated in approximately 24% of those receiving 2.5 mg of letrozole and in approximately 16% of those receiving megestrol acetate. Median duration of response had not been reached with 2.5 mg of letrozole; median duration of response for megestrol acetate was reached at 18 months.
Letrozole was generally well tolerated. The most common adverse effects with the 2.5-mg dose were musculoskeletal pain, nausea, headache, arthralgia, fatigue, vomiting, and dyspnea.
Mechanism of Aromatase Inhibitors in Breast Cancer
Unlike antiestrogens, such as tamoxifen, which block estrogen from stimulating cancer cells by binding to estrogen receptors in those cells, aromatase inhibitors reduce the amount of estrogen circulating in the body. Letrozole binds to the enzyme aromatase and inhibits it from converting a precursor hormoneandrostenedioneto estrogen in such tissues as fat, liver, and muscle.
Women whose disease cannot be controlled by antiestrogen therapy may be switched to other hormonal therapies, including aromatase inhibitors. In postmenopausal women, the aromatase pathway is the primary source of estrogen production. According to a recent report, nearly 120,000 US women are living with advanced breast cancer. Of these women, the majority are postmenopausal (over the age of 50 years ).