根據(jù)于2012年8月2日發(fā)表在New England Journal of Medicine期刊上的SWOG S0226臨床試驗結(jié)果，相比于只接受阿那曲唑(anastrozole)標(biāo)準(zhǔn)治療的患有激素受體陽性的轉(zhuǎn)移性乳腺癌的女性而言,，聯(lián)合接受阿那曲唑(anastrozole)和氟維司群(fulvestrant)治療能夠延長她們的平均存活時間多于6個月(從41.3個月提升至47.7個月),。
對這些病人而言,，這種聯(lián)合療法也延長疾病惡化時間(從13.5個月提升至15個月),。無疾病惡化的存活時間是這項試驗的主要療效指標(biāo)，而總存活時間是次要療效指標(biāo),。
阿那曲唑和氟維司群都是抗雌激素藥物,。阿那曲唑抑制身體產(chǎn)生促進(jìn)腫瘤形成的雌激素，而氟維司群不僅阻斷雌激素用來促進(jìn)腫瘤細(xì)胞生長和復(fù)制的受體,，而且還加速這些受體的降解,。來自美國加州大學(xué)伊文醫(yī)療中心(Irvine Medical Center)的研究員Rita Mehta博士和她的同事們猜測這兩種不同作用模式結(jié)合在一起時可能要比單獨時更好地治療激素受體陽性的轉(zhuǎn)移性乳腺癌。
在這項研究中,，研究人員也報道,，41%只服用阿那曲唑的病人換用氟維司群治療，當(dāng)疾病惡化時,，再服用阿那曲唑,，治療結(jié)果提示著聯(lián)用這兩種藥物而不是先后使用將產(chǎn)生顯著性提高的存活率。
研究人員注意到,，盡管在這項試驗中,，女性病人服用的氟維司群劑量每月2250mg只是當(dāng)前標(biāo)準(zhǔn)治療所使用的劑量的一半，他們觀察到聯(lián)用這兩種藥物導(dǎo)致病人存活率提高,。他們建議未來的臨床試驗需要研究一下聯(lián)用高劑量氟維司群和諸如阿那曲唑之類的芳香化酶抑制劑(aromatase inhibitor)的療效,。(生物谷：Bioon.com)
本文編譯自http://medicalxpress.com/news/2012-08-anastrozole- fulvestrant-combo-drug-metastatic.html
doi: 10.1056/NEJMoa1201622
PMC:
PMID:
"Combination Anastrozole and Fulvestrant in Metastatic Breast Cancer
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.)
