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Combination treatment with fulvestrant and various cytotoxic agents (doxorubicin, paclitaxel, docetaxel, vinorelbine, and 5-fluorouracil) has a synergistic effect in estrogen receptor-positive breast cancer.
Ikeda, Hirokuni; Taira, Naruto; Nogami, Tomohiro; Shien, Kazuhiko; Okada, Masanori; Shien, Tadahiko; Doihara, Hiroyoshi; Miyoshi, Shinichiro.
Afiliação
  • Ikeda H; Department of Cancer and Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
Cancer Sci ; 102(11): 2038-42, 2011 Nov.
Article em En | MEDLINE | ID: mdl-21801281
ABSTRACT
Patients with estrogen receptor (ER)-positive breast cancers have a better prognosis than those with ER-negative breast cancers, but often have low sensitivity to chemotherapy and a limited survival benefit. We have previously shown a combination effect of taxanes and fulvestrant and suggested that this treatment may be useful for ER-positive breast cancer. In this study, we evaluated the effects of combinations of hormone drugs and chemotherapeutic agents. In vitro, the effects of combinations of five chemotherapeutic agents (doxorubicin, paclitaxel, docetaxel, vinorelbine, and 5-fluorouracil) and three hormone drugs (fulvestrant, tamoxifen, and 4-hydroxytamoxifen) were examined in ER-positive breast cancer cell lines using CalcuSyn software. Changes in chemoresistant factors such as Bcl2, multidrug resistance-associated protein 1, and microtubule-associated protein tau were also examined after exposure of the cells to hormone drugs. In vivo, tumor sizes in mice were evaluated after treatment with docetaxel or doxorubicin alone, fulvestrant alone, and combinations of these agents. Combination treatment with fulvestrant and all five chemotherapeutic agents in vitro showed synergistic effects. In contrast, tamoxifen showed an antagonistic effect with all the chemotherapeutic agents. 4-Hydroxytamoxifen showed an antagonistic effect with doxorubicin and 5-fluorouracil, but a synergistic effect with taxanes and vinorelbine. Regarding chemoresistant factors, Bcl2 and microtubule-associated protein tau were downregulated by fulvestrant. In vivo, a combination of fulvestrant and docetaxel had a synergistic effect on tumor growth, but fulvestrant and doxorubicin did not show this effect. In conclusion, fulvestrant showed good compatibility with all the evaluated chemotherapeutic agents, and especially with docetaxel, in vitro and in vivo.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia; Neoplasias da Mama/patologia; Carcinoma Ductal de Mama/patologia; Estradiol/análogos & derivados; Estrogênios; Neoplasias Hormônio-Dependentes/patologia; Animais; Antineoplásicos Hormonais/farmacologia; Protocolos de Quimioterapia Combinada Antineoplásica/antagonistas & inibidores; Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico; Docetaxel; Doxorrubicina/administração & dosagem; Doxorrubicina/antagonistas & inibidores; Doxorrubicina/farmacologia; Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos; Ensaios de Seleção de Medicamentos Antitumorais; Sinergismo Farmacológico; Estradiol/administração & dosagem; Estradiol/farmacologia; Moduladores de Receptor Estrogênico/farmacologia; Feminino; Fluoruracila/administração & dosagem; Fluoruracila/antagonistas & inibidores; Fluoruracila/farmacologia; Fulvestranto; Humanos; Camundongos; Camundongos Nus; Proteínas de Neoplasias/biossíntese; Paclitaxel/administração & dosagem; Paclitaxel/antagonistas & inibidores; Paclitaxel/farmacologia; Distribuição Aleatória; Tamoxifeno/análogos & derivados; Tamoxifeno/farmacologia; Taxoides/administração & dosagem; Taxoides/antagonistas & inibidores; Taxoides/farmacologia; Células Tumorais Cultivadas/efeitos dos fármacos; Vimblastina/administração & dosagem; Vimblastina/análogos & derivados; Vimblastina/antagonistas & inibidores; Vimblastina/farmacologia; Vinorelbina; Ensaios Antitumorais Modelo de Xenoenxerto

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Protocolos de Quimioterapia Combinada Antineoplásica / Carcinoma Ductal de Mama / Estradiol / Estrogênios / Neoplasias Hormônio-Dependentes Idioma: En Ano de publicação: 2011 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Protocolos de Quimioterapia Combinada Antineoplásica / Carcinoma Ductal de Mama / Estradiol / Estrogênios / Neoplasias Hormônio-Dependentes Idioma: En Ano de publicação: 2011 Tipo de documento: Article