Exemestane is an oral aromatase inhibitor (but also known uniquely as an aromatase inactivator) used in the adjuvant treatment of hormonally-responsive (also called hormone-receptor-positive, estrogen-responsive) breast cancer in postmenopausal women.
Exemestane (trade name Aromasin) is a medication used to treat breast cancer. It is a member of the class of antiestrogens known as aromatase inhibitors. Some breast cancers require estrogen to grow. Those cancers have estrogen receptors (ERs), and are called ER-positive. They may also be called estrogen-responsive, hormonally-responsive, or hormone-receptor-positive. Aromatase is an enzyme that synthesizes estrogen. Aromatase inhibitors block the synthesis of estrogen. This lowers the estrogen level, and slows the growth of cancers.
Exemestane is indicated for the adjuvant treatment of postmenopausal women with estrogen-receptor positive early breast cancer who have received two to three years of tamoxifen and are switched to it for completion of a total of five consecutive years of adjuvant hormonal therapy. US FDA approval was in October 2005.
Exemestane is also indicated for the treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy.
The most common side effects (more than 10% of patients) are hot flashes and sweating, which are typical of estrogen deficiency as caused by exemestane, and also insomnia, headache, and joint pain. Nausea and fatigueare mainly observed in patients with advanced breast cancer.
An occasional decrease in lymphocytes has been observed in approximately 20% of patients receiving Aromasin, particularly in patients with pre-existing lymphopenia. 
Exemestane has androgenic properties similarly to formestane and can produce androgenic side effects such as acne and weight gain, although these are generally associated with supratherapeutic dosages of the drug.
Single doses of up to at least 32-fold (800 mg), as well as continuous therapy with 24-fold (600 mg) the usual daily dose are well tolerated. No life-threatening overdosing is known in humans, but only in animal studies with 2000- to 4000-fold doses (adjusted to body surface area).
Exemestane is an oral steroidal aromatase inhibitor that is used in ER-positive breast cancer in addition to surgery and/or radiation in post-menopausal women.
The main source of estrogen is the ovaries in premenopausal women, while in post-menopausal women most of the body’s estrogen is produced via the conversion of androgens into estrogen by the aromatase enzyme in the peripheral tissues (i.e. adipose tissue like that of the breast) and a number of sites in the brain. Estrogen is produced locally via the actions of the aromatase enzyme in these peripheral tissues where it acts locally. Any circulating estrogen in post-menopausal women as well as men is the result of estrogen escaping local metabolism and entering the circulatory system.
Exemestane is an irreversible, steroidal aromatase inactivator of type I, structurally related to the natural substrate 4-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, an effect also known as “suicide inhibition.” By being structurally similar to enzyme targets, exemestane permanently binds to the enzymes, preventing them from converting androgen into estrogen.
Exemestane is quickly absorbed from the gut, but undergoes a strong first-pass effect in the liver. Highest blood plasma concentrations are reached after 1.2 hours in breast cancer patients and after 2.9 hours in healthy subjects. Maximal aromatase inhibition occurs after two to three days. 90% of the absorbed substance are bound to plasma proteins. The liver enzyme CYP3A4 oxidizes the methylidene group in position 6, and the 17-keto group (on the five-membered ring) is reduced by aldo-keto reductases to an alcohol. Of the resulting metabolites, 40% are excreted via the urine and 40% via the feces within a week. The original substance accounts for only 1% of excretion in the urine. The terminal half-life is 24 hours.
Exemestane is known chemically as 6-methylideneandrosta-1,4-diene-3,17-dione. Like the aromatase inhibitors formestane and atamestane, exemestane is a steroid that is structurally similar to 4-androstenedione, the natural substrate of aromatase. It is distinguished from the natural substance only by the methylidene group in position 6 and an additional double bond in position 1.
Exemestane has been used in doping to raise luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels, which in turn increases the ratio of male over female sexual hormones and so improves performance. The drug also counteracts gynecomastia as well as fat and water retention following excessive aromatase production due to testosterone doping.
Oral exemestane 25 mg/day for 2–3 years of adjuvant therapy was generally more effective than 5 years of continuous adjuvant tamoxifen in the treatment of postmenopausal women with early-stage estrogen receptor-positive/unknown receptor status breast in a large well-designed trial. Preliminary data from the open-label TEAM trial comparing exemestane with tamoxifen indicated in 2009 that exemestane 25 mg/day is also effective in the primary adjuvant treatment of early-stage breast cancer in postmenopausal women.
Interim phase III trial results in 2011 showed that adding everolimus to exemestane therapy against advanced breast cancer can significantly improve progression-free survival compared with exemestane therapy alone.
A Phase III trial was reported in 2011, concluding that the use of exemestane in postmenopausal women at an increased risk for breast cancer reduced the incidence of invasive breast cancer. In 4,560 women, after 35 months, the administration of exemestane at a dose of 25 mg/day resulted in a 65% reduction in the risk of breast cancer compared with placebo; annual incidence rates were 0.19% and 0.55%, respectively (hazard ratio: 0.35; 95% CI [0.18-0.70]; p = 0.002).
Exemestane is an oral aromatase inhibitor (but also known uniquely as an aromatase inactivator) used in the adjuvant treatment of hormonally-responsive (also called hormone-receptor-positive, estrogen-responsive) breast cancer in postmenopausal women. An aim in the treatment of hormone-receptor-positive patients in preventing recurrence is to lower estrogen levels that this breast cancer thrives on. The main source of estrogen is the ovaries in premenopausal women, while in post-menopausal women most of the body’s estrogen is produced in the adrenal gland from the conversion of androgens into estrogen by the aromatase enzyme. Exe mes tane 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, an effect also known as “suicide inhibition.” In other words, Exe mes tane, by being structurally similar to the target of the enzymes, permanently binds to those enzymes, thereby preventing them from ever completing their task of converting androgens into estrogens. The estrogen suppression rate for exemestane varies from 85% for estradiol (E2) to 95% for estrone (E1). Packaged as a research chemical, 30ml vial x 10mg per ml.
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