Formestane is a synthetic steroidal aromatase inhibitor, historically marketed as Lentaron. It played a role in treating hormone-sensitive conditions, marking a significant step in managing diseases influenced by estrogen levels.
Understanding Aromatase and Estrogen
Aromatase is an enzyme found in various tissues throughout the body, including fat, muscle, and the brain. Its primary function involves a biochemical process called aromatization, which converts androgen hormones into estrogens. Specifically, aromatase facilitates the transformation of androstenedione into estrone and testosterone into estradiol.
Estrogen hormones are naturally occurring steroids that influence numerous bodily functions in both males and females. These include regulating the menstrual cycle, maintaining bone density, and affecting cardiovascular health. However, in certain medical conditions, an excess of estrogen can promote the growth of specific types of cells, particularly in some breast cancers. In postmenopausal women, peripheral tissues become the main source of estrogen through the action of aromatase.
How Formestane Works
Formestane acts as a steroidal aromatase inhibitor, specifically classified as a Type I inhibitor. This means it structurally resembles the natural substrates of the aromatase enzyme, such as androstenedione. Formestane binds irreversibly to the active site of the aromatase enzyme.
Once bound, formestane forms a stable complex with the enzyme, leading to its permanent inactivation. This irreversible binding prevents the aromatase enzyme from converting androgens into estrogens. By reducing the overall activity of aromatase, formestane effectively lowers the production of estrogen in the body.
Formestane’s Role in Breast Cancer Treatment
Formestane was developed and primarily used for the treatment of hormone-receptor-positive breast cancer, particularly in postmenopausal women. In these types of cancers, the cancer cells possess receptors that can bind to estrogen, and the presence of estrogen can stimulate their growth and proliferation. Reducing estrogen levels can therefore slow or halt the progression of the disease.
For postmenopausal women, the majority of estrogen is produced in peripheral tissues through the aromatase enzyme, rather than in the ovaries. By inhibiting aromatase, formestane decreases the amount of estrogen available to fuel the growth of these cancer cells. It was often considered as a second-line hormonal therapy, sometimes used after treatments like tamoxifen. In clinical trials, formestane demonstrated its ability to significantly lower estrogen levels, which contributed to its anti-tumor effects in patients with advanced breast cancer.
Administration and Common Side Effects
Formestane was typically administered through intramuscular injection. The usual dosage involved a 250 mg injection given every two weeks, commonly into the gluteal muscle. This method of administration was necessary because formestane has poor oral bioavailability, meaning it is not well absorbed when taken by mouth.
Common side effects included hot flashes, which are a frequent symptom of reduced estrogen levels, and nausea. Patients might also experience reactions at the injection site, such as pain or swelling. Fatigue was another reported side effect.
Formestane’s Current Place in Medicine
While formestane was an important early aromatase inhibitor, its use has largely been superseded by newer agents in many clinical settings. More recent aromatase inhibitors, such as anastrozole, letrozole, and exemestane, offer advantages like oral administration, which improves patient convenience. These newer drugs are also often more selective in their action or demonstrate improved efficacy in clinical trials.
Despite being less commonly used today, formestane might still be considered in specific circumstances or in regions where access to newer alternatives is limited. Its historical significance as one of the first selective, steroidal aromatase inhibitors remains, paving the way for more advanced treatments for hormone-sensitive breast cancer.