Description
Formestane is a potent aromatase inhibitor launched in the UK as a second-line
endocrine treatment for breast cancer. As a synthetic derivative of androstanedione, the
natural substrate for the biosynthesis of estrogen by the enzyme aromatase, formastane
selectively inhibits aromatase and binds to its steroid receptor site to cause a rapid and
sustained fall in circulating estrogen level and, therefore, inhibits tumor growth. In patients
with existing bulky primary tumors, formestane effectively reduces the size of the tumors.
Formastane has apparent tolerability advantages and less side effects than other agents such
as aminoglutethimide.
Originator
Ciba-Geigy (Switzerland)
History
Formestane is a second-generation steroidal aromatase inhibitor, and the first one to reach clinical use during the early 1990s[1].
Definition
ChEBI: A 17-oxo steroid that is androst-4-ene-3,17-dione in which the hydrogen at position 4 is replaced by a hydroxy group. Formestane was the first selective, type I steroidal aromatase inhibitor, suppressing oestrogen production from anabolic steroids or proho
mones. It was formerly used in the treatment of oestrogen-receptor positive breast cancer in post-meopausal women. As it has poor oral bioavailability, it had to be administered by (fortnightly) intramuscular injection. It fell out of use with the subseque
t development of cheaper, orally active aromatase inhibitors. Formestane is listed by the World Anti-Doping Agency as a substance prohibited from use by athletes.
Mechanism of action
Aromatase inhibitors such as formestane and letrozole reduce plasma estradiol levels by inhibiting the conversion of testosterone to estrogen. This compound was first described as a competitive inhibitor, but subsequent evidence proved that its binding to aromatase was irreversible. Hence, it is a suicide inhibitor. In the dog, but not rodents, this results in Leydig cell hypertrophy and hyperplasia. This is thought to be due to the differential sensitivity of the pituitary feedback mechanism to estrogens and androgens in the different species[1-2].
References
[1] Avenda?o C, et al. Anticancer Drugs That Inhibit Hormone Action. Medicinal Chemistry of Anticancer Drugs, 2008; 53-91.0
[2] Berczi I, et al. Biologically Controlled Mutations are Right for Evolution. Insights to Neuroimmune Biology, 2016; 217-241.
