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接受厄洛替尼和贝伐珠单抗治疗的上消化道癌患者组织中的生物标志物。

Biomarkers in tissue from patients with upper gastrointestinal cancers treated with erlotinib and bevacizumab.

机构信息

Department of Oncology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.

出版信息

Cancer Biol Ther. 2011 Apr 15;11(8):732-9. doi: 10.4161/cbt.11.8.14889.

Abstract

Malignancies in the upper gastrointestinal (UGI) tract are amongst the most aggressive cancers and only few treatment options exist. We have recently analysed data from a phase II trial where patients with UGI cancers were treated with erlotinib and bevacizumab. The combination therapy could not be recommended in an unselected population of patients with chemo-refractory UGI cancer. However, a subpopulation of patients did benefit from the therapy. In this prospectively planned biomarker study we investigated vascular endothelial growth factor A (VEGF-A), VEGF receptor 2 (VEGFR-2) and epidermal growth factor receptor (EGFR) by immunohistochemistry and KRAS mutation status detected by PCR as potential predictors of effect of therapy. High VEGF-A expression was correlated to longer overall survival (HR: 0.8, 95%CI: 0.7-0.9) and high VEGFR-2 expression to shorter progression free survival (HR: 1.4, 95%CI: 1.0-1.9). EGFR expression and KRAS mutation status were not correlated to response or survival. We conclude that VEGF-A and VEGFR-2 could potentially be predictive markers in patients with UGI cancers treated with erlotinib and bevacizumab.

摘要

上消化道(UGI)恶性肿瘤是最具侵袭性的癌症之一,目前仅有少数治疗选择。我们最近分析了一项 II 期临床试验的数据,该试验中接受厄洛替尼和贝伐珠单抗治疗的 UGI 癌症患者。联合治疗不能推荐用于化疗耐药的 UGI 癌症患者的未选择人群。然而,一部分患者确实从治疗中获益。在这项前瞻性计划的生物标志物研究中,我们通过免疫组织化学检测血管内皮生长因子 A(VEGF-A)、血管内皮生长因子受体 2(VEGFR-2)和表皮生长因子受体(EGFR),并通过 PCR 检测 KRAS 突变状态,作为治疗效果的潜在预测因子。高 VEGF-A 表达与更长的总生存期相关(HR:0.8,95%CI:0.7-0.9),高 VEGFR-2 表达与更短的无进展生存期相关(HR:1.4,95%CI:1.0-1.9)。EGFR 表达和 KRAS 突变状态与反应或生存无关。我们得出结论,VEGF-A 和 VEGFR-2 可能是接受厄洛替尼和贝伐珠单抗治疗的 UGI 癌症患者的潜在预测标志物。

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