Fulvestrant is an estrogen receptor antagonist. It blocks and degrades estrogen receptors and is used for the treatment of hormone receptor‑positive, HER2‑negative advanced or metastatic breast cancer.
I. Drug Overview
What is Fulvestrant?
(1) Fulvestrant (brand name: FASLODEX) is a prescription drug administered by intramuscular injection.
(2) It is an endocrine therapy agent, mainly used for the treatment of hormone receptor‑positive (HR+) advanced breast cancer.
Indicated Populations
(1) Postmenopausal women with HR‑positive, HER2‑negative advanced breast cancer who have not received prior endocrine therapy.
(2) Postmenopausal women with HR‑positive advanced breast cancer with disease progression after endocrine therapy.
(3) Use in combination with ribociclib, palbociclib, or abemaciclib for HR‑positive, HER2‑negative advanced or metastatic breast cancer.
Dosage Form and Strength
Fulvestrant is available as a prefilled syringe, each containing 250 mg/5 mL solution. Two injections are usually required to achieve the recommended dose of 500 mg.
II. Mechanism of Action
Estrogen Receptor Antagonism and Degradation
Fulvestrant competitively binds to the estrogen receptor with an affinity similar to estradiol. It can:
(1) Block the stimulatory effect of estrogen on cancer cells.
(2) Downregulate estrogen receptor protein levels in breast cancer cells.
(3) Inhibit the growth of estrogen‑sensitive and tamoxifen‑resistant human breast cancer cells.
Antitumor Activity
(1) In in vivo studies, fulvestrant delayed the formation of human breast cancer cell xenografts, inhibited the growth of established tumors, and also showed inhibitory effects on tamoxifen‑resistant breast tumors.
(2) Unlike estrogen, fulvestrant showed no agonist‑like effects in uterine trophic tests in mice and rats.
III. Drug Interactions
No Clinically Relevant Interactions
Fulvestrant does not significantly inhibit major CYP enzymes (including CYP1A2, 2C9, 2C19, 2D6, and 3A4) in vitro. Clinical studies confirmed that:
(1) Coadministration with ketoconazole, a CYP3A4 inhibitor, does not affect the pharmacokinetics of fulvestrant.
(2) Coadministration with rifampicin, a CYP3A4 inducer, showed no changes in pharmacokinetics.
(3) There are no clinically relevant drug interactions when combined with palbociclib, abemaciclib, or ribociclib.
Therefore, no dose adjustment is required when coadministered with CYP3A4 inhibitors or inducers.
IV. Precautions
Common Adverse Reactions
Adverse reactions with an incidence ≥ 5% include:
(1) Injection site pain, nausea, bone pain, arthralgia.
(2) Headache, back pain, fatigue, pain in extremities.
(3) Hot flushes, vomiting, decreased appetite, asthenia.
(4) Musculoskeletal pain, cough, dyspnea, constipation.
Laboratory Abnormalities
(1) Elevated liver enzymes (ALT, AST, ALP) occurred in 15% of patients.
(2) The incidence of Grade 3–4 elevations was approximately 1–2%, and was not dose‑related.
Injection Site Precautions
(1) Care should be taken to avoid sciatic nerve injury when injecting into the gluteus maximus muscle.
(2) If numbness, tingling, or weakness in the leg occurs after injection, prompt medical attention should be sought.
