12月29日,，據(jù)每日科學(xué)：靶向性藥物,，用于阻斷或破壞參與腫瘤生長(zhǎng)的特定分子,，已被證明能有效的治療多種癌癥,。一項(xiàng)由婦科腫瘤組織(GOG)指導(dǎo)的新的三期臨床試驗(yàn)顯示,，一種名叫貝伐單抗（Avastin，阿瓦斯?。┑陌邢蛐辕煼苡行У匮泳?fù)砥诼殉舶┑倪M(jìn)程,。目前,，新確診的晚期卵巢癌患者通常是接受手術(shù)和化療,，但是新研究提供了另一項(xiàng)治療途徑。
臨床實(shí)驗(yàn)的結(jié)果發(fā)表于12月29日新英格蘭醫(yī)學(xué)期刊（New England Journal of Medicine）上,。
"這種方法可以看做卵巢癌治療的第三個(gè)重要組成部分,，"醫(yī)學(xué)博士Robert A.Burger說(shuō)，她是GOG研究的首席研究員及?？怂拱┌Y中心女性癌癥中心的主任,。"多年來(lái)我們一直采取手術(shù)管理和細(xì)胞毒性化療相結(jié)合的療法，但我們還沒(méi)有真正看到一種所謂的根本性的療法,。這代表著一種新的方式來(lái)控制疾病,。"
安慰劑對(duì)照試驗(yàn)，由國(guó)家癌癥研究所贊助,，從336個(gè)地區(qū)（主要是美國(guó),，也有加拿大、韓國(guó),、日本）招募了1873位之前未進(jìn)行治療的晚期卵巢癌患者,。患者要么是III期卵巢癌不能經(jīng)手術(shù)完全除去或IV期卵巢癌,，隨機(jī)的分配成3組,。接受貝伐單抗結(jié)合化療并在接下來(lái)的日子中接受額外的10個(gè)月貝伐單抗治療的患者，癌癥進(jìn)展的平均時(shí)間是14.1個(gè)月,，而對(duì)照組（只接受化療和安慰劑治療并持續(xù)接受安慰劑）為10.3個(gè)月,。減少乳腺癌進(jìn)展風(fēng)險(xiǎn)的凈有效率為28%。接受貝伐單抗及化療但后期不繼續(xù)使用貝伐單抗的患者,，癌癥無(wú)進(jìn)展生存時(shí)間平均為11.2個(gè)月,。
國(guó)家癌癥研究所估計(jì)，在2011年有近22000名女性被診斷為卵巢癌,，超過(guò)15000名女性死于這種疾病,。在癌癥未擴(kuò)散前診斷出的患者,，5年相對(duì)存活率約為93%（相對(duì)存活率只計(jì)算癌癥所致，不計(jì)算其他原因所致的死亡）,。但卵巢癌是隱襲的--早期癥狀,，像腹脹、腹痛,、進(jìn)食困難,，這些都是其他一些疾病的典型癥狀，很容易錯(cuò)診為不具威脅性,。女性通常不會(huì)意識(shí)到她們患上了這種疾病,，知道它開(kāi)始擴(kuò)散。在62%的心法病例中,，患者的癌癥已經(jīng)擴(kuò)散到很遠(yuǎn)的地方了,，5年生存率低于27%。
貝伐單抗已被FDA批準(zhǔn)用于治療一些類型的癌癥,，如結(jié)腸癌,、肺癌、腎癌,、腦癌,；其用于轉(zhuǎn)移性乳腺癌的加速審批最近被FDA撤銷。這種藥物是通過(guò)與血管內(nèi)皮生長(zhǎng)因子VEGF的結(jié)合來(lái)起作用,，VEGF是特定腫瘤產(chǎn)生的一種蛋白質(zhì),，用于幫助新生血管的形成為腫瘤提供養(yǎng)分。新生血管的生長(zhǎng)稱為血管生成,，而貝伐單抗即是一種血管生成抑制劑,。
"貝伐單抗阻斷了VEGF，它是卵巢癌進(jìn)展過(guò)程中非常重要的生長(zhǎng)因子,，"Burger說(shuō),，"我們已經(jīng)看到這種藥物在疾病復(fù)發(fā)的患者中也有效"。
血管生成發(fā)生在宿主和腫瘤的接觸面上,，這使得它稱為非常有吸引力的治療靶標(biāo),，Burger說(shuō)，他執(zhí)導(dǎo)了GOG研究的II期,，使用貝伐單抗治療復(fù)發(fā)性卵巢癌,。他說(shuō)，不同的卵巢癌在顯微鏡下可能會(huì)一樣,，但是在生物學(xué)上卻是不同的,，這意味著它們對(duì)治療有不同的反應(yīng)。
在新英格蘭醫(yī)學(xué)期刊的論文中，Burger和他的共同作者指出,，另一項(xiàng)主要在歐洲開(kāi)展的卵巢癌臨床試驗(yàn)（ICON7）得到了積極的結(jié)果,，即用貝伐單抗結(jié)合化療并持續(xù)使用貝伐單抗7個(gè)月。
這篇發(fā)表于NEJM上的論文的共同作者還包括Mark F.Brady（Roswell Park癌癥研究所）,、Michael A.Bookman（Arizon癌癥中心）,、Gini F.Fleming（芝加哥大學(xué)）、Bradley J.Monk（Creighton大學(xué)醫(yī)學(xué)院）,、Helen Huang（Roswell Park）,、Robert S.Mannel（俄克拉荷馬州大學(xué)健康科學(xué)中心）、Howard D.Homesley（維克深林大學(xué)醫(yī)學(xué)院）,、Jdrrrey Fowler（俄亥俄州大學(xué)詹姆斯腫瘤醫(yī)院）,、Benjamin E.Greer（西雅圖癌癥護(hù)理聯(lián)盟）、Matthew Boente（明尼蘇達(dá)州腫瘤學(xué)和血液學(xué)研究所）,、Michael J.Birrer（哈佛醫(yī)學(xué)院及馬薩組賽州總醫(yī)院）,、Sharon X.Liang（北岸-長(zhǎng)島猶太醫(yī)療系統(tǒng)）。（生物谷bioon.com）
doi:10.1056/NEJMoa1104390
PMC:
PMID:
Incorporation of Bevacizumab in the Primary Treatment of Ovarian Cancer
Robert A. Burger, Mark F. Brady, Michael A. Bookman, Gini F. Fleming, Bradley J. Monk, Helen Huang, Robert S. Mannel, Howard D. Homesley, Jeffrey Fowler, Benjamin E. Greer, Matthew Boente, Michael J. Birrer, Sharon X. Liang
BACKGROUND: Vascular endothelial growth factor is a key promoter of angiogenesis and disease progression in epithelial ovarian cancer. Bevacizumab, a humanized anti–vascular endothelial growth factor monoclonal antibody, has shown single-agent activity in women with recurrent tumors. Thus, we aimed to evaluate the addition of bevacizumab to standard front-line therapy.
METHODS: In our double-blind, placebo-controlled, phase 3 trial, we randomly assigned eligible patients with newly diagnosed stage III (incompletely resectable) or stage IV epithelial ovarian cancer who had undergone debulking surgery to receive one of three treatments. All three included chemotherapy consisting of intravenous paclitaxel at a dose of 175 mg per square meter of body-surface area, plus carboplatin at an area under the curve of 6, for cycles 1 through 6, plus a study treatment for cycles 2 through 22, each cycle of 3 weeks' duration. The control treatment was chemotherapy with placebo added in cycles 2 through 22; bevacizumab-initiation treatment was chemotherapy with bevacizumab (15 mg per kilogram of body weight) added in cycles 2 through 6 and placebo added in cycles 7 through 22. Bevacizumab-throughout treatment was chemotherapy with bevacizumab added in cycles 2 through 22. The primary end point was progression-free survival.
RESULTS: Overall, 1873 women were enrolled. The median progression-free survival was 10.3 months in the control group, 11.2 in the bevacizumab-initiation group, and 14.1 in the bevacizumab-throughout group. Relative to control treatment, the hazard ratio for progression or death was 0.908 (95% confidence interval [CI], 0.795 to 1.040; P=0.16) with bevacizumab initiation and 0.717 (95% CI, 0.625 to 0.824; P<0.001) with bevacizumab throughout. At the time of analysis, 76.3% of patients were alive, with no significant differences in overall survival among the three groups. The rate of hypertension requiring medical therapy was higher in the bevacizumab-initiation group (16.5%) and the bevacizumab-throughout group (22.9%) than in the control group (7.2%). Gastrointestinal-wall disruption requiring medical intervention occurred in 1.2%, 2.8%, and 2.6% of patients in the control group, the bevacizumab-initiation group, and the bevacizumab-throughout group, respectively.
CONCLUSIONS: The use of bevacizumab during and up to 10 months after carboplatin and paclitaxel chemotherapy prolongs the median progression-free survival by about 4 months in patients with advanced epithelial ovarian cancer. (Funded by the National Cancer Institute and Genentech; ClinicalTrials.gov number, NCT00262847.)
