Current and future perspectives on fulvestrant.
Fulvestrant, an estrogen receptor antagonist with no known agonist effects, is effective and well tolerated in the treatment of hormone-sensitive breast cancer after antiestrogen failure in postmenopausal women. Numerous phase II and III clinical trials of fulvestrant that are designed to build on its efficacy in breast cancer and explore its value in other tumors are ongoing or in the final planning stage. Favorable safety, dose-response, and pharmacokinetic data led to the initiation of clinical trials to evaluate loading and higher doses with the aim of building on the well-defined efficacy of fulvestrant. Recently reported results of phase II trials by the North Central Cancer Treatment Group and the Swiss Group for Clinical Cancer Research support the clinical activity of fulvestrant after recurrence or progression on a nonsteroidal aromatase inhibitor, and 2 international phase III trials are ongoing in this setting. As a first-line treatment for metastatic disease, fulvestrant is currently being evaluated in combination with anastrozole versus anastrozole alone in 2 phase III trials, 1 by the Southwest Oncology Group and the other being conducted mainly in Scandinavia. Preclinical data have also led to randomized phase II trials of fulvestrant in combination with the epidermal growth factor receptor tyrosine kinase inhibitor, gefitinib, and the HER2/neu-targeted antibody trastuzumab. Additional phase II and III trials are currently evaluating fulvestrant plus tipifarnib, Theratope vaccine, or the dual kinase inhibitor, GW572016. Although fulvestrant is undergoing robust clinical development as a treatment for breast cancer, investigation of this agent in other types of solid tumors has only just begun.
Gradishar
William J
WJ
Robert H. Lurie Comprehensive Cancer Center and NorthWestern University Feinberg School of Medicine, 676 North St. Clair Street, Chicago, IL 60611, USA. w-gradishar@northwestern.edu
Sahmoud
Tarek
T
D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D009570:Nitriles / Q000627:therapeutic use; D011960:Receptors, Estrogen / Q000378:metabolism; D014230:Triazoles / Q000627:therapeutic use
D018931:Antineoplastic Agents, Hormonal; D009570:Nitriles; D011960:Receptors, Estrogen; D014230:Triazoles; D000077267:Fulvestrant; D000077384:Anastrozole; D004958:Estradiol