Department of Oncology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Cancer Biol Ther. 2011 Apr 15;11(8):732-9. doi: 10.4161/cbt.11.8.14889.
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.
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。