Exemestane (Aromasin)

[MaNiCC]

Exemestane (trade name Aromasin) is an oral steroidal aromatase inhibitor 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. 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, an effect also known as “suicide inhibition.” In other words, Exemestane, 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).

Systematic (IUPAC) name
Identifiers
CAS number 107868-30-4
ATC code L02BG06
PubChem CID 60198
DrugBank APRD00144

Chemical data
Formula C20H24O2
Mol. mass 296.403 g/mol

Pharmacokinetic data
Bioavailability ~60%
Protein binding 90%
Half-life 27 hours

Therapeutic considerations
Pregnancy cat. D
Legal status Rx only
Routes Oral
Clinical uses
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.
Exemestane is indicated for the treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy.
Therapeutic Efficacy
Oral exemestane 25mg/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. Prelimanary data from the open-label TEAM trial comparing exemestane with tamoxifen indicates that exemestane 25mg/day is also effective in the primary adjuvant treatment of early-stage breast cancer in postmenopausal women.