Phase II Trial of Exemestane in Combination With Fulvestrant in Postmenopausal Women With Advanced, Hormone-Responsive Breast Cancer
| Autor: | Charles L. Shapiro, Bhuvaneswari Ramaswamy, Rachel M. Layman, Ewa Mrozek, Larry J. Schaaf, Xiaobai Li, Susan Ottman |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Hormone Responsive Oncology Cancer Research medicine.medical_specialty Phases of clinical research Breast Neoplasms Article chemistry.chemical_compound Breast cancer Exemestane Internal medicine Antineoplastic Combined Chemotherapy Protocols Humans Medicine Insulin-Like Growth Factor I Fulvestrant Aged Aged 80 and over Postmenopausal women Estradiol business.industry Middle Aged medicine.disease Metastatic breast cancer Androstadienes Postmenopause Insulin-Like Growth Factor Binding Protein 3 Receptors Estrogen chemistry Female Receptors Progesterone business Steroidal Aromatase Inhibitor medicine.drug |
| Zdroj: | Clinical Breast Cancer. 12:151-156 |
| ISSN: | 1526-8209 |
| Popis: | Exemestane, the irreversible steroidal aromatase inhibitor, and fulvestrant, the pure estrogen antagonist, are active as single drugs in postmenopausal women with advanced hormone-responsive breast cancer. We designed a phase II study with the purpose of determining whether combining these 2 drugs with different and potentially complementary mechanisms of action will improve the clinical benefit.Forty postmenopausal women with hormone-responsive advanced breast cancer received intramuscular injection of fulvestrant 250 mg every 28 days in combination with daily exemestane 25 mg until disease progression. We examined the influence of fulvestrant on exemestane pharmacokinetics and the effect of exemestane and fulvestrant on serum IGF-1 (insulin-like growth factor 1) and IGFBP-3 (IGF-binding protein 3) levels.The observed proportion of patients free of progressive disease at 6 months after the initiation of treatment with exemestane and fulvestrant was 50%, a rate similar to that achieved with single-agent exemestane or fulvestrant in the first- or second-line setting. Pharmacokinetics parameters showed that coadministration of fulvestrant did not result in clinically relevant changes in exemestane plasma concentrations. A comparison of IGF-1 and IGFBP-3 levels demonstrated the increase of 35% and 12%, respectively, in mean levels from baseline to day 120.The combination of exemestane and fulvestrant did not improve clinical benefit. The observed lack of improved efficacy was not related to altered drug exposure. |
| Databáze: | OpenAIRE |
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