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A good drug made better: the Fulvestrant Dose Response Story

Robertson, John F.R., Lindemann, Justin, Garnett, Sally, Anderson, Elizabeth, Nicholson, Robert I., Kuter, Irene and Gee, Julia Margaret Wendy 2014. A good drug made better: the Fulvestrant Dose Response Story. Clinical Breast Cancer 14 (6) , pp. 381-389. 10.1016/j.clbc.2014.06.005

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Abstract

Sequential use of endocrine therapies remains the cornerstone of treatment for hormone receptor-positive advanced breast cancer, prior to use of cytotoxic chemotherapy for unresponsive disease. Fulvestrant is an estrogen receptor (ER) antagonist approved for treatment of postmenopausal women with ER+ advanced breast cancer following failure of prior antiestrogen therapy. Initially approved at a monthly dose of 250 mg, the recommended fulvestrant dose was revised to 500 mg (500 mg/month plus 500 mg on Day 14 of Month 1) following demonstration of improved progression-free survival versus fulvestrant 250 mg. We have reviewed the dose-dependent effects of fulvestrant, both from a retrospective combined analysis of dose-dependent reduction of tumor biomarkers in the pre-surgical setting (three previously reported studies: Study 18, NEWEST [Neoadjuvant Endocrine Therapy for Women with Estrogen-Sensitive Tumors] and Trial 57), and from a review of clinical studies for advanced breast cancer in postmenopausal women. Analysis of pre-surgical data revealed a consistent dose-dependent effect for fulvestrant on tumor biomarkers, with increasing fulvestrant dose resulting in greater reductions in ER, progesterone receptor and Ki67 labeling index. The dose-dependent biological effect corresponds with the dose-dependent clinical efficacy observed in the treatment of advanced breast cancer following failure of prior antiestrogen therapy. Although it remains to be determined in a Phase III trial, cross-trial comparisons suggest a dose-dependent relationship for fulvestrant as first-line treatment for advanced breast cancer. Overall, biological and clinical data demonstrate a strong dose-dependent relationship for fulvestrant, supporting the efficacy benefit seen with fulvestrant 500 mg over the 250 mg dose.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords: advanced breast cancer; endocrine therapy; estrogen receptor; postmenopausal; tumor biomarkers
Additional Information: Pdf uploaded in accordance with publisher's policy at http://www.sherpa.ac.uk/romeo/issn/1526-8209/ [accessed 03/11/2014]
Publisher: Elsevier
ISSN: 1526-8209
Date of Acceptance: 17 June 2014
Last Modified: 01 Mar 2019 15:41
URI: http://orca-mwe.cf.ac.uk/id/eprint/65915

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