Fulvestrant is a synthetic estrogen receptor antagonist. Unlike tamoxifen (which has partial agonist effects) and the aromatase inhibitors (which reduce the estrogen available to tumor cells), fulvestrant binds competitively to estrogen receptors in breast cancer cells, resulting in estrogen receptor deformation and decreased estrogen binding. In vitro studies indicate that fulvestrant reversibly inhibits the growth of tamoxifen-resistant, estrogen-sensitive, human breast cancer cell lines. (NCI04)
Fulvestrant is a steroidal antiestrogen that is used in the treatment of hormone-receptor-positive metastatic breast cancer. Fulvestrant therapy can be associated with serum enzyme elevations but has yet to be linked to instances of clinically apparent acute liver injury in the published literature.
Mechanism of Action of Fulvestrant
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.
Fulvestrant, a 7(alpha)-alkylsulfinyl analog of estradiol, is an estrogen antagonist. Data from animal studies indicate that fulvestrant does not possess estrogen-agonist activity. The drug competitively binds to and downregulates estrogen receptors in human breast cancer cells. Fulvestrant has been shown to inhibit the growth of tamoxifen-resistant as well as estrogen-sensitive human breast cancer (MCF-7) cell lines in vitro and in vivo. Data from studies in animals indicate that the drug also may block the uterotropic action of estradiol. Fulvestrant does not appear to exhibit peripheral steroidal effects in postmenopausal women, as evidenced by an absence of appreciable changes in plasma concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) after receiving 250 mg of fulvestrant monthly.
Indications of Fulvestrant
- For the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following anti-estrogen therapy.
- Fulvestrant is a steroidal antiestrogen that is used in the treatment of hormone-receptor-positive metastatic breast cancer. Fulvestranttherapy can be associated with serum enzyme elevations but has yet to be linked to instances of clinically apparent acute liver injury in the published literature.
- Refractory, advanced Breast cancer
- Refractory, metastatic Breast cancer
- It is indicated as monotherapy for the treatment of estrogen receptor positive, locally advanced or metastatic breast cancer in postmenopausal women not previously treated with endocrine therapy, or with disease relapse on or after adjuvant antiestrogen therapy, or disease progression on antiestrogen therapy in combination with palbociclib for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer in women who have received prior endocrine therapy. In pre- or perimenopausal women, the combination treatment with palbociclib should be combined with a luteinizing hormone-releasing hormone (LHRH) agonist.
Contraindications of Fulvestrant
- Low amount of magnesium in the blood
- The high amount of calcium in the blood
- Low amount of potassium in the blood
- Decreased blood platelets
- Decreased white blood cells
- Very rapid heartbeat – torsades de pointes
- Prolonged QT interval on EKG
- Abnormal EKG with QT changes from birth
- Obstruction of a blood vessel by a blood clot
- Overgrowth of the Uterine Lining
- Pregnancy
- A mother who is producing milk and breastfeeding
- Increased risk of bleeding due to a clotting disorder
- Decreased Blood Platelets
- Liver problems
- Pregnancy
- A mother who is producing milk and breastfeeding
- Allergies to Fulvestrant
Dosage of Fulvestrant
Strengths: 50 mg/mL
Breast Cancer
Monotherapy
- 500 mg IM into the buttocks (gluteal area) slowly (1 to 2 minutes per injection) as two 5 mL injections, one in each buttock, on days 1, 15, 29 and once monthly thereafter
Combination Therapy
- In combination with palbociclib or abemaciclib: 500 mg IM into the buttocks (gluteal area) slowly (1 to 2 minutes per injection) as two 5 mL injections, one in each buttock, on days 1, 15, 29 and once monthly thereafter.
Side Effects of Fulvestrant
More Common
- Bloating or swelling of the face, arms, hands, lower legs, or feet
- Difficult or labored breathing
- tightness in the chest
- Back pain
- bladder pain
- bloody or cloudy urine
- body aches or pain
- bone pain
- burning, crawling, itching, numbness, prickling, “pins and needles”, or tingling feelings
- depression
- diarrhea
- difficulty having a bowel movement
- difficulty with moving
- dizziness
- dryness or soreness of the throat
- feeling faint, dizzy, or lightheaded
- feeling of warmth or heat
Common
- are allergic to fulvestrant or any ingredients of the medication
- are breast-feeding
- are pregnant
- headache
- hot flashes
- loss of appetite
- mild pain, redness, or swelling around the site of the injection
- nausea
- rash
- vomiting
- weakness
Drug Interactions of Fulvestrant
Fulvestrant may interact with following drugs, supplements & may change the efficacy of the drug
- celecoxib
- dapsone
- echinacea
- fluoxetine
- ganciclovir
- glipizide
- glyburide
- interferon
- ketamine
- leflunomide
- leucovorin
- levamisole
- live vaccines (e.g., BCG, yellow fever)
- losartan
- montelukast
- nateglinide
- other cancer medications (including but not limited to cytarabine, flucytosine, methotrexate)
- pimecrolimus
- phenytoin
- sulfamethoxazole
- tacrolimus
- tamoxifen
- tolbutamide
- trimethoprim
- voriconazole
- warfarin
Pregnancy Category of Fulvestrant
AU TGA pregnancy category: D
US FDA pregnancy category: N (Not assigned)
US FDA pregnancy category: N (Not assigned)
Pregnancy
This medication should not be used during pregnancy. It may cause severe harm to the developing baby if it is used by the mother during childhood. If you become pregnant while taking this medication, contact your doctor immediately.
Lactation
It is not known if fulvestrant passes into breast milk. If you are a breast-feeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding. The safety and effectiveness of using this medication have not been established for children.
References
