Introduction
Fulvestrant is a drug treatment of hormone receptor (HR)-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor. While it is used as monotherapy for the treatment of breast cancers, it is also used in combination with alpelisib for the treatment of HR-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, advanced or metastatic breast cancer
Uses
Fulvestrant is an estrogen receptor antagonist used to treat HR+ breast cancer that may also be HER2-.
For the treatment of hormone receptor positive metastatic breast cancer in postmenopausal women with disease progression following anti-estrogen therapy, as monotherapy or in combination with other antineoplastic agents.
Associated Conditions
Pharmacodynamics
Fulvestrant for intramuscular administration is an estrogen receptor antagonist without known agonist effects.
Mechanism of Action
Fulvestrant competitively and reversibly binds to estrogen receptors present in cancer cells and achieves its anti-estrogen effects through two separate mechanisms. First, fulvestrant binds to the receptors and downregulates them so that estrogen is no longer able to bind to these receptors. Second, fulvestrant degrades the estrogen receptors to which it is bound. Both of these mechanisms inhibit the growth of tamoxifen-resistant as well as estrogen-sensitive human breast cancer cell lines.
Volume of Distribution
- 3 to 5 L/kg
Protein Binding
99% (mainly VLDL, LDL, and HDL)
Route of Elimination
Fulvestrant was rapidly cleared by the hepatobiliary route with excretion primarily via the feces (approximately 90%). Renal elimination was negligible (less than 1%).
Half Life
40 days
Toxicity
There is no clinical experience with overdosage in humans.
Food Interactions
No interactions found.
Dosage
A dose of 250 mg is recommended in patients with moderate hepatic impairment to be administered intramuscularly into the buttock (gluteal area) slowly (1-2 minutes) as one 5 mL injection on Days 1, 15, 29, and once monthly thereafter.
Pediatric Use: Safety and effectiveness in pediatric patients have not been established.
