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腾讯登录NEJM：联用阿那曲唑和氟维司群更有利于治疗转移性乳腺癌
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阿那曲唑(anastrozole)结构式，图片来自维基共享资源。</p>
根据于2012年8月2日发表在<em>New England Journal of Medicine</em>期刊上的SWOG S0226临床试验结果，相比于只接受阿那曲唑(anastrozole)标准治疗的患有激素受体阳性的转移性乳腺癌的女性而言，联合接受阿那曲唑(anastrozole)和氟维司群(fulvestrant)治疗能够延长她们的平均存活时间多于6个月(从41.3个月提升至47.7个月)。
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对这些病人而言，这种联合疗法也延长疾病恶化时间(从13.5个月提升至15个月)。无疾病恶化的存活时间是这项试验的主要疗效指标，而总存活时间是次要疗效指标。
阿那曲唑和氟维司群都是抗雌激素药物。阿那曲唑抑制身体产生促进肿瘤形成的雌激素，而氟维司群不仅阻断雌激素用来促进肿瘤细胞生长和复制的受体，而且还加速这些受体的降解。来自美国加州大学伊文医疗中心(Irvine Medical Center)的研究员Rita Mehta博士和她的同事们猜测这两种不同作用模式结合在一起时可能要比单独时更好地治疗激素受体阳性的转移性乳腺癌。
在这项研究中，研究人员也报道，41%只服用阿那曲唑的病人换用氟维司群治疗，当疾病恶化时，再服用阿那曲唑，治疗结果提示着联用这两种药物而不是先后使用将产生显著性提高的存活率。
研究人员注意到，尽管在这项试验中，女性病人服用的氟维司群剂量每月2250mg只是当前标准治疗所使用的剂量的一半，他们观察到联用这两种药物导致病人存活率提高。他们建议未来的临床试验需要研究一下联用高剂量氟维司群和诸如阿那曲唑之类的芳香化酶抑制剂(aromatase inhibitor)的疗效。
本文编译自<a href="http://medicalxpress.com/news/2012-08-anastrozole-fulvestrant-combo-drug-metastatic.html">http://medicalxpress.com/news/2012-08-anastrozole- fulvestrant-combo-drug-metastatic.html</a>
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<a title="" href="http://dx.doi.org/10.1056/NEJMoa1201622" target="_blank">doi: 10.1056/NEJMoa1201622</a>
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<br/><strong>"Combination Anastrozole and Fulvestrant in Metastatic Breast Cancer</strong><br/>
Rita S. Mehta, M.D., William E. Barlow, Ph.D., Kathy S. Albain, M.D., Ted A. Vandenberg, M.D., Shaker R. Dakhil, M.D., Nagendra R. Tirumali, M.D., Danika L. Lew, M.A., Daniel F. Hayes, M.D., Julie R. Gralow, M.D., Robert B. Livingston, M.D., and Gabriel N. Hortobagyi, M.D.
BACKGROUND The aromatase inhibitor anastrozole inhibits estrogen synthesis. Fulvestrant binds and accelerates degradation of estrogen receptors. We hypothesized that these two agents in combination might be more effective than anastrozole alone in patients with hormone-receptor (HR)–positive metastatic breast cancer. METHODS Postmenopausal women with previously untreated metastatic disease were randomly assigned, in a 1:1 ratio, to receive either 1 mg of anastrozole orally every day (group 1), with crossover to fulvestrant alone strongly encouraged if the disease progressed, or anastrozole and fulvestrant in combination (group 2). Patients were stratified according to prior or no prior receipt of adjuvant tamoxifen therapy. Fulvestrant was administered intramuscularly at a dose of 500 mg on day 1 and 250 mg on days 14 and 28 and monthly thereafter. The primary end point was progression-free survival, with overall survival designated as a prespecified secondary outcome. RESULTS The median progression-free survival was 13.5 months in group 1 and 15.0 months in group 2 (hazard ratio for progression or death with combination therapy, 0.80; 95% confidence interval [CI], 0.68 to 0.94; P=0.007 by the log-rank test). The combination therapy was generally more effective than anastrozole alone in all subgroups, with no significant interactions. Overall survival was also longer with combination therapy (median, 41.3 months in group 1 and 47.7 months in group 2; hazard ratio for death, 0.81; 95% CI, 0.65 to 1.00; P=0.05 by the log-rank test), despite the fact that 41% of the patients in group 1 crossed over to fulvestrant after progression. Three deaths that were possibly associated with treatment occurred in group 2. The rates of grade 3 to 5 toxic effects did not differ significantly between the two groups. CONCLUSIONS The combination of anastrozole and fulvestrant was superior to anastrozole alone or sequential anastrozole and fulvestrant for the treatment of HR-positive metastatic breast cancer, despite the use of a dose of fulvestrant that was below the current standard. (Funded by the National Cancer Institute and AstraZeneca; SWOG ClinicalTrials.gov number, NCT00075764.)
<br/>来源：生物谷
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阿那曲唑(anastrozole)结构式，图片来自维基共享资源。</p>
根据于2012年8月2日发表在<em>New England Journal of Medicine</em>期刊上的SWOG S0226临床试验结果，相比于只接受阿那曲唑(anastrozole)标准治疗的患有激素受体阳性的转移性乳腺癌的女性而言，联合接受阿那曲唑(anastrozole)和氟维司群(fulvestrant)治疗能够延长她们的平均存活时间多于6个月(从41.3个月提升至47.7个月)。
<!--more-->
对这些病人而言，这种联合疗法也延长疾病恶化时间(从13.5个月提升至15个月)。无疾病恶化的存活时间是这项试验的主要疗效指标，而总存活时间是次要疗效指标。
阿那曲唑和氟维司群都是抗雌激素药物。阿那曲唑抑制身体产生促进肿瘤形成的雌激素，而氟维司群不仅阻断雌激素用来促进肿瘤细胞生长和复制的受体，而且还加速这些受体的降解。来自美国加州大学伊文医疗中心(Irvine Medical Center)的研究员Rita Mehta博士和她的同事们猜测这两种不同作用模式结合在一起时可能要比单独时更好地治疗激素受体阳性的转移性乳腺癌。
在这项研究中，研究人员也报道，41%只服用阿那曲唑的病人换用氟维司群治疗，当疾病恶化时，再服用阿那曲唑，治疗结果提示着联用这两种药物而不是先后使用将产生显著性提高的存活率。
研究人员注意到，尽管在这项试验中，女性病人服用的氟维司群剂量每月2250mg只是当前标准治疗所使用的剂量的一半，他们观察到联用这两种药物导致病人存活率提高。他们建议未来的临床试验需要研究一下联用高剂量氟维司群和诸如阿那曲唑之类的芳香化酶抑制剂(aromatase inhibitor)的疗效。
本文编译自<a href="http://medicalxpress.com/news/2012-08-anastrozole-fulvestrant-combo-drug-metastatic.html">http://medicalxpress.com/news/2012-08-anastrozole- fulvestrant-combo-drug-metastatic.html</a>
<div id="ztload">
<div> </div>
<div>
<div>
<img src="http://www.bioon.com/biology/UploadFiles/201204/2012041012314317.jpg" alt="" width="113" height="149" border="0" />
<a title="" href="http://dx.doi.org/10.1056/NEJMoa1201622" target="_blank">doi: 10.1056/NEJMoa1201622</a>
PMC:
PMID:
</div>
<div>
<br/><strong>"Combination Anastrozole and Fulvestrant in Metastatic Breast Cancer</strong><br/>
Rita S. Mehta, M.D., William E. Barlow, Ph.D., Kathy S. Albain, M.D., Ted A. Vandenberg, M.D., Shaker R. Dakhil, M.D., Nagendra R. Tirumali, M.D., Danika L. Lew, M.A., Daniel F. Hayes, M.D., Julie R. Gralow, M.D., Robert B. Livingston, M.D., and Gabriel N. Hortobagyi, M.D.
BACKGROUND The aromatase inhibitor anastrozole inhibits estrogen synthesis. Fulvestrant binds and accelerates degradation of estrogen receptors. We hypothesized that these two agents in combination might be more effective than anastrozole alone in patients with hormone-receptor (HR)–positive metastatic breast cancer. METHODS Postmenopausal women with previously untreated metastatic disease were randomly assigned, in a 1:1 ratio, to receive either 1 mg of anastrozole orally every day (group 1), with crossover to fulvestrant alone strongly encouraged if the disease progressed, or anastrozole and fulvestrant in combination (group 2). Patients were stratified according to prior or no prior receipt of adjuvant tamoxifen therapy. Fulvestrant was administered intramuscularly at a dose of 500 mg on day 1 and 250 mg on days 14 and 28 and monthly thereafter. The primary end point was progression-free survival, with overall survival designated as a prespecified secondary outcome. RESULTS The median progression-free survival was 13.5 months in group 1 and 15.0 months in group 2 (hazard ratio for progression or death with combination therapy, 0.80; 95% confidence interval [CI], 0.68 to 0.94; P=0.007 by the log-rank test). The combination therapy was generally more effective than anastrozole alone in all subgroups, with no significant interactions. Overall survival was also longer with combination therapy (median, 41.3 months in group 1 and 47.7 months in group 2; hazard ratio for death, 0.81; 95% CI, 0.65 to 1.00; P=0.05 by the log-rank test), despite the fact that 41% of the patients in group 1 crossed over to fulvestrant after progression. Three deaths that were possibly associated with treatment occurred in group 2. The rates of grade 3 to 5 toxic effects did not differ significantly between the two groups. CONCLUSIONS The combination of anastrozole and fulvestrant was superior to anastrozole alone or sequential anastrozole and fulvestrant for the treatment of HR-positive metastatic breast cancer, despite the use of a dose of fulvestrant that was below the current standard. (Funded by the National Cancer Institute and AstraZeneca; SWOG ClinicalTrials.gov number, NCT00075764.)
<br/>来源：生物谷
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