Originally published as JCO Early Release 10.1200/JCO.2002.10.057 on July 1 2002

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Fulvestrant, Formerly ICI 182,780, Is as Effective as Anastrozole in Postmenopausal Women With Advanced Breast Cancer Progressing After Prior Endocrine Treatment

From the Christie Hospital, Manchester, City Hospital, Nottingham, and AstraZeneca, Macclesfield, Cheshire, United Kingdom; Instituto Portugues De Oncologia De Coimbra, Coimbra, Portugal; Odborny Lecebny Ustav Onkologie A Pneumologie, Nova Ves Plod Plesi, Czech Republic; Institut Bergonie, Bordeaux, France; Haematologisch/Onkologische Praxis, Hamburg, Germany; University Hospital Leuven, Leuven, Belgium; and Norwegian Radium Hospital, Oslo, Norway.

Address reprint requests to A. Howell, MD, Department of Medical Oncology, Christie Hospital National Health Service Trust, Wilmslow Rd, Manchester M20 4BX, United Kingdom; email (A.H.’s assistant): maria.parker{at}christie-tr.nwest.nhs.ukto

PURPOSE: To compare the efficacy and tolerability of fulvestrant (formerly ICI 182,780) and anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment.

PATIENTS AND METHODS: Patients (n = 451) with advanced breast cancer were randomized to receive fulvestrant 250 mg as a once-monthly (one x 5 mL) intramuscular injection or an oral dose of anastrozole 1 mg in this open, parallel-group, multicenter trial. The primary end point was time to progression (TTP). Secondary end points included objective response (OR) rates, defined as complete response (CR) or partial response (PR), duration of response (DOR), and tolerability.

RESULTS: Patients were followed for a median period of 14.4 months. In terms of TTP, fulvestrant was as effective as anastrozole (hazard ratio, 0.98; confidence interval [CI], 0.80 to 1.21; P = .84). Median TTP was 5.5 months for fulvestrant and 5.1 months for anastrozole. OR rates showed a numerical advantage for fulvestrant (20.7%) over anastrozole (15.7%) (odds ratio, 1.38; CI, 0.84 to 2.29; P = .20). Clinical benefit rates (CR + PR + stable disease 24 weeks) were 44.6% for fulvestrant and 45.0% for anastrozole. Median DOR was 15.0 months for fulvestrant and 14.5 months for anastrozole. Both treatments were well tolerated, with 3.2% and 1.3% of fulvestrant- and anastrozole-treated patients, respectively, withdrawn from treatment because of an adverse event.

CONCLUSION: Fulvestrant was as effective as anastrozole. These data confirm that fulvestrant is an additional, effective, and well-tolerated treatment for advanced breast cancer in postmenopausal women whose disease progressed on prior endocrine therapy.

This article was published ahead of print at www.jco.org.

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				P. F. Bross, A. Baird, G. Chen, J. M. Jee, R. T. Lostritto, D. E. Morse, L. A. Rosario, G. M. Williams, P. Yang, A. Rahman, et al. Fulvestrant in Postmenopausal Women with Advanced Breast Cancer Clin. Cancer Res., October 1, 2003; 9(12): 4309 - 4317. [Abstract] [Full Text] [PDF]

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				V. C. Jordan Is Tamoxifen the Rosetta Stone for Breast Cancer? J Natl Cancer Inst, March 5, 2003; 95(5): 338 - 340. [Full Text] [PDF]

				A. U. Buzdar Pharmacology and Pharmacokinetics of the Newer Generation Aromatase Inhibitors Clin. Cancer Res., January 1, 2003; 9(1): 468S - 472S. [Abstract] [Full Text] [PDF]

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