Trastuzumab In HER2-Positive Metastatic Gastric Cancer
Trastuzumab In HER2-Positive Metastatic Gastric Cancer
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DOI：
10.2165/11205900-000000000-00000
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发表时间：
2010-01-01
期刊：
影响因子：
11.5
通讯作者：
McKeage, Kate
中科院分区：
文献类型：
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作者：
Croxtall, Jamie D.;McKeage, Kate
曲妥珠单抗是一种重组人源化 IgG(1) 单克隆抗体，针对人表皮生长因子受体 2 型 (HER2) 的胞外结构域，可抑制 HER2 依赖性肿瘤细胞增殖和存活。曲妥珠单抗在体外和体内均抑制过表达 HER2 的胃癌细胞的增殖。22 例患者中观察到 HER2 阳性表达（定义为免疫组织化学 3+ 或荧光原位杂交阳性）。在开放标签、多中心、III 期 ToGA 试验中，对近 4000 名转移性胃癌患者进行随机筛选。在 HER2 阳性转移性胃癌患者 (n = 584) 中，接受静脉曲妥珠单抗联合化疗（包括顺铂和氟尿嘧啶或卡培他滨）的患者的中位总生存期（主要终点）明显长于 ToGA 试验中单独接受化疗的患者。与单独化疗相比，曲妥珠单抗联合化疗的总体缓解率显着更高，疾病进展的中位时间和无进展生存的中位时间也显着更长。一般来说，曲妥珠单抗和化疗的联合治疗在转移性胃癌患者中的耐受性相对较好，没有新的或意外的不良事件的报告
Trastuzumab is a recombinant humanized IgG(1) monoclonal antibody directed against the extracellular domain of the human epidermal growth factor receptor type 2 (HER2) that inhibits HER2-dependent tumour cell proliferation and survival Proliferation of gastric cancer cells overexpressing HER2 is inhibited by trastuzumab in vitro and in vivoHER2-positive expression (defined as immunohistochemistry 3+ or fluorescence in situ hybridization-positive) was observed in 22 1% of almost 4000 metastatic gastric cancers in patients who were screened for randomization in the open-label, multicentre, phase III ToGA trialIn patients with HER2-positive metastatic gastric cancer (n = 584), median overall survival (primary endpoint) was significantly longer for recipients of intravenous trastuzumab plus chemotherapy (comprising cisplatin and either fluorouracil or capecitabine) than in those receiving chemotherapy alone in the ToGA trialFurthermore, the overall response rate was significantly higher and the median time to disease progression and median time of progression-free survival were also significantly longer with trastuzumab plus chemotherapy than with chemotherapy aloneIn general, combination therapy with trastuzumab and chemotherapy was relatively well tolerated in patients with metastatic gastric cancer with no reports of new or unexpected adverse events