Currently Enrolling Trials
Aromasin, a new drug to treat post-menopausal advanced breast cancer in patients for whom treatment with tamofixen was ineffective, has been shown to inhibit the production of estrogen, upon which some breast cancer cells depend. Furthermore, studies indicate that Aromasin, which reduces the risk of tumor progression by 18 percent and the risk of death by 23 percent, is more beneficial than the hormone therapy, megestrol acetate.
In post-menopausal women, the principle source of estrogen comes from the conversion of adrenal and ovarian androgens to estrogens by the aromatase (exemestane) enzyme. For post-menopausal women with hormone-dependent breast cancer, Aromasin serves as an aromatase inhibitor. As a result, the concentrations of estrogen, on which breast cancer cells may depend, are lowered. This estrogen-depriving process nicknamed, "suicide inhibition," is irreversible. However, it does not affect other enzymes involved in the steroidogenic pathway up to a concentration at least 600 times higher than that inhibiting the aromatase enzyme.
Aromasin should not be administered to premenopausal women. Neither should it be coadministered with estrogen-containing agents.
Pregnant women should not take Aromasin, as it could pose a potential hazard to the fetus, and could cause potential loss of the pregnancy.
Aromasin has not yet been tested for pediatric patients.
A phase III, double blind, randomized study was conducted for 769 post-menopausal patients whose breast cancer had metastasized (spread). The study compared the effects of Aromasin versus those of megestrol acetate on survival, tumor reduction, and duration of disease stabilization. Patients taking megestrol acetate had a median survival (estimated time at which 50 percent of the patients were still alive) of approximately 28 months, while patients taking Aromasin had a median survival significantly longer than 28 months (p< 0.039). Moreover, the progression of cancer was delayed longer in patients taking Aromasin (4.7 months) than in patients taking megestrol acetate (3.8 months). Also, 15 percent of patients treated with Aromasin experienced at least a 50 percent or greater reduction in the size of the tumor or a complete disappearance of all known lesions. This suggested a possible advantage over the 12.4 percent of patients treated with megestrol acetate who experienced this effect, although the difference was not statistically significant. Finally, the regiment for taking Aromasin is one 25mg pill taken daily, versus the 40mg pill of megestrol acetate taken four times daily. Based on the study's results, researchers are confident that Aromasin provides greater benefit than megestrol acetate.
In clinical trials, any adverse effects were generally described as mild to moderate. Some Aromasin use was associated with low-grade nausea, hot-flashes, fatigue, increased sweating, and increased appetite. However, only 7.6% of patients experienced undesirable weight gain (lower than the rate caused by magestrol acetate).
Aromasin should not be administered to premenopausal women. Neither should it be coadministered with estrogen-containing agents. Pregnant women should not take Aromasin, as it could pose a potential hazard to the fetus, and could cause potential loss of the pregnancy.
Mechanism of Action
Exemestane is an irreversible, steroidal aromatase inactivator, structurally related to the natural substrate androstenedione. It acts as a false substrate for the aromatase enzyme and is processed to an intermediate that binds irreversibly to the active site of the enzyme causing its inactivation. Exemestane significantly lowers circulating estrogen concentrations in postmenopausal women, but has no detectable effect on adrenal biosynthesis of corticosteroids or aldosterone. (FDA Label)