P&T Portfolio - - Faslodex

August 19, 2002

Information on Faslodex (Fulvestrant)used to treat breast cancer in women who did not respond well to tamoxifen.

 

HEALTH-SYSTEM EDITION
P&T PORTFOLIO

Generic name

Fulvestrant

Proprietary name/manufacturer

Faslodex / AstraZeneca

FDA-approved indication

Treatment of hormone receptor positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy

Pharmacology

Fulvestrant is an estrogen receptor antagonist without known agonist effects. Fulvestrant competes with endogenous estrogen for estrogen receptor binding and downregulates the estrogen receptor protein in human breast cancer cells. The relative binding affinity of fulvestrant is 89% that of estradiol, while that of tamoxifen is 2.5%. In vitro studies have demonstrated that fulvestrant is a reversible inhibitor of the growth of tamoxifen-resistant, as well as estrogen-sensitive, human breast cancer (MCF-7) cell lines.

Efficacy

The approval of fulvestrant was based upon data from two controlled clinical trials conducted in North America and Europe. The trials compared fulvestrant with anastrozole in postmenopausal women with locally advanced or metastatic breast cancer who had exhibited disease progression after previous therapy with an antiestrogen or progestin. Study results indicate that there was no significant difference in time to disease progression, objective response rates, or survival time between the two agents. Limited retrospective data also suggest that fulvestrant produces a similar but longer duration of response compared with megestrol in patients with tamoxifen-resistant breast cancer, but more study is needed. Efficacy data for the use of fulvestrant in premenopausal women with advanced breast cancer are not available.

Fulvestrant is similar in efficacy to anastrozole for the treatment of postmenopausal women with locally advanced or metastatic breast cancer.

Pharmacokinetics

Protein binding99%
Volume of distribution3 to 5L/kg
MetabolismOxidation, aromatic hydroxylation, and conjugation in liver to several metabo lites. Cytochrome P-450 3A4 is involved
ExcretionFeces (90%)
Half-life (steady state)40 days

Contraindications

• Pregnant women

• Hypersensitivity to the drug or any product components

Warnings

• May cause fetal harm when administered to pregnant women

• Bleeding diatheses, thrombocytopenia, or in patients on anticoagulants

Adverse effects

The most common (10%-26%) adverse effects were:

• Nausea

• Asthenia

• Pain

• Vasodilation

• Bone pain

• Pharyngitis

• Headache

• Dyspnea

• Back pain

• Vomiting

• Constipation

• Diarrhea

• Abdominal pain

• Injection site pain

• Increased cough

Dose

250 mg intramuscularly every month as a single 5-ml injection or two concurrent 2.5-ml injections

Conclusion/comments

Fulvestrant is a pure estrogen antagonist that has been shown to be effective as second-line therapy in postmenopausal women with advanced breast cancer. It appears to be comparable in efficacy to anastrozole in postmenopausal patients with tamoxifen-resistant advanced breast cancer. Fulvestrant offers the convenience of a once-monthly intramuscular injection and provides another treatment option in these patients. Ongoing trials are investigating fulvestrant as first-line therapy for advanced breast cancer and for the treatment of premenopausal women with breast cancer.

Published July 2002. Content based on medical literature and product information available at that time.

 

 



P&T Portfolio - - Faslodex.

Drug Topics

2002;16:HSE22.