Fulvestrant: Pharmacologic profile versus existing endocrine agents for the treatment of breast cancer

OBJECTIVE: To compare the pharmacologic profile of fulvestrant with that of tamoxifen and the aromatase inhibitors with respect to the choice of treatment for advanced breast cancer (ABC). DATA SOURCES: Principal literature and review articles were obtained from MEDLINE (1991-March 2006). Key search terms included fulvestrant, tamoxifen, aromatase inhibitors, pharmacology, and breast cancer. Further data sources were identified from the bibliographies of selected articles. STUDY SELECTION AND DATA EXTRACTION: English-language preclinical and clinical research and review articles reporting pharmacologic and safety data for fulvestrant, tamoxifen, and the aromatase inhibitors were evaluated to identify relevant information. Randomized clinical trial data were preferred over preclinical or Phase I and II trial data. DATA SYNTHESIS: A total of 52 clinical papers (including 10 reviews) and 17 clinical abstracts were evaluated reporting results from controlled Phase I-III studies and pilot studies. Eleven preclinical papers (including 2 reviews) and 6 preclinical abstracts were also included. Fulvestrant has little effect on sex hormone endocrinology, bone metabolism, and lipid biochemistry and appears unlikely to be the subject or cause of CYP3A4-mediated drug interactions. Tamoxifen has a protective effect on bone (due to its partial estrogen agonist activity) and reduces plasma low-density lipoprotein cholesterol but increases triglyceride levels. The aromatase inhibitors have variable effects on lipid profiles and sex hormone endocrinology but have detrimental effects on bone due to inhibition of estrogen synthesis. Drug interactions have been noted between tamoxifen and anticoagulants and tamoxifen and aromatase inhibitors, which may be due to CYP-mediated mechanisms. CONCLUSIONS: Fulvestrant appears to have little effect on sex hormone endocrinology, bone metabolism, and lipid biochemistry and is unlikely to be subject to or the cause of CYP3A4-mediated drug-drug interactions. As such, fulvestrant represents a valuable new endocrine therapy for the treatment of ABC and broadens the options available to clinicians in the treatment of this disease.