Exemestane

Exemestane is a prescription drug used for the treatment of breast cancer. It belongs to a family of anticancer drugs known as aromatase inhibitors. Other members of this family include anastrozole (Arimidex) and letrozole (Femara). Aromatase inhibitors prevent the synthesis of estrogen in postmenopausal women. Many breast cancers are dependent on estrogen for survival. Breast cancer that is dependent on estrogen is called estrogen-receptor positive or hormone-dependent. The U.S. Food and Drug Administration approved exemestane in October 1999.

A technician is performing a test on breast tissue to determine whether it expresses the estrogen receptor. Breast tissue is in a petri dish. Exemestane is used for breast cancers that express the estrogen receptor. Source: National Cancer Institute

Other Names

Exemestane is marketed as Aromasin by Pfizer.

Uses

Exemestane is used to treat postmenopausal women with estrogen-receptor positive early breast cancer who have received two to three years of tamoxifen. Exemestane replaces tamoxifen and is used to complete total of five consecutive years of hormonal therapy. This regimen–tamoxifen followed by exemestane–is used as adjuvant therapy. Adjuvant therapy is used as a follow-up to another intervention. In the case of breast cancer, the adjuvant therapy usually follows surgery.

Exemestane is also indicated for the treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy.

How Exemestane is Taken

Exemestane is available in tablets of 25 mg. The recommended dose is one 25 mg tablet once daily after a meal.

In postmenopausal women with early breast cancer who have been treated with tamoxifen for 2–3 years, exemestane is used to complete five years of adjuvant therapy even if there is no evidence of recurrence or cancer in the unaffected breast. For patients with advanced breast cancer, exemestane treatment continues until tumor regression.

How Exemestane Works

Estrogen is a female sex hormone that plays a major role in sexual maturation and reproductive health. After menopause however, when a woman stops menstruating, estrogen levels in the body drop dramatically. However, estrogen continues to be produced in postmenopausal women, and it is this residual estrogen that may contribute to the growth and development of some breast cancers. Breast cancer cells that are stimulated by estrogen are called hormone-dependent or estrogen-receptor positive. The latter term is used because the surfaces of these cells express estrogen receptors. In many women with these cancers, estrogen deprivation has been shown to be an effective treatment.

The enzyme aromatase converts androgens (hormones that control male characteristics) to estrogens. Even in postmenopausal women, aromatase activity is sufficient to maintain estrogen, albeit at lower levels than those in premenopausal women. Exemestane inhibits aromatase and significantly lowers circulating estrogen levels. This, in turn, deprives the breast cancer cells of their estrogen stimulus.

How the Body Affects Exemestane

Exemestane is very rapidly absorbed into the body, and peak levels in the blood occur approximately 1.2 hours after a single dose in postmenopausal women with breast cancer. Exemestane is extensively metabolized in the liver by an enzyme called CYP3A4. A dose of exemestane is excreted in the urine and feces in equal amounts.

Side Effects

Below are the most common side effects of exemestane:

• hot flushes
• hair loss
• high blood pressure
• nausea
• depression
• diarrhea
• dermatitis (skin inflammation)
• headache
• muscle aches

Risks and Precautions

Exemestane is used in postmenopausal women only. Use during pregnancy could produce birth defects.

Drug Interactions

Because exemestane is metabolized by CYP3A4, the dose may need to be modified when given with drugs that increase the activity of this enzyme. Drugs that increase the activity of CYP3A4 include carbamazepine (Tegretol), phenytoin (Dilantin), and rifampacin. These CYP3A4 inducers would lower the concentration of exemestane in the blood and could alter the drug’s effectiveness or safety.

Research

Disease-free and survival rates were examined in a multicenter trial of postmenopausal women treated with either tamoxifen or exemestane following 2–3 years of tamoxifen.^[1] The women were given either exemestane or tamoxifen for the remainder of their five-year adjuvant therapy. Exemestane reduced the risk of recurrent disease by 24% compared to tamoxifen. Exemestane had reduced the risk of death by 17% compared to tamoxifen treatment.

The B-33 trial examined the effectiveness of exemestane given for five years following five years of treatment with tamoxifen in women with early-stage breast cancer. The study showed that exemestane increased the probability of disease-free survival 32% after 30 months of treatment.^[2] Disease-free survival in women treated with exemestane was 91%, whereas it was 89% in women not given the drug. Exemestane had no effect on overall mortality rates.

References

1. ↑ Coombes RC, Kilburn LS, Snowdon CF, et al. Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet. 2007 Feb 17;369(9561):559-70. Erratum in: Lancet. 2007 Mar 17;369(9565):906. Abstract
2. ↑ LF, Robidoux A, Hoehn JL, et al. Benefit from exemestane as extended adjuvant therapy after 5 years of adjuvant tamoxifen: intention-to-treat analysis of the National Surgical Adjuvant Breast And Bowel Project B-33 trial. J Clin Oncol. 2008 Apr 20;26(12):1965-71. Abstract | Press Release

External Links

FDA: Patient Information Shesurvivldisease-freeTheet