Digestive Oncology, University Hospitals Leuven and KULeuven, Leuven, Belgium.
Target Oncol. 2013 Jun;8(2):83-96. doi: 10.1007/s11523-013-0281-x. Epub 2013 May 5.
Despite a decrease in incidence and mortality, colorectal cancer (CRC) still represents the second leading cause of cancer worldwide. Recurrence following surgery and adjuvant treatment and the metastatic disease are still a major problem with a median overall survival of approximately 24 months. Nevertheless, there has been an improvement in outcome due to the introduction into clinical practice of new cytotoxic and targeted agents. The targeted agents that have improved the efficacy of the available chemotherapeutic regimens in CRC are the ones that target the vascular endothelial growth factor (VEGF) and the epidermal growth factor receptor (EGFR). In particular, bevacizumab, a recombinant humanized monoclonal antibody against VEGF, cetuximab, and panitumumab, two monoclonal antibodies that target the EGFR, have been approved for the treatment of metastatic CRC (mCRC). While for anti-EGFR agents, predictive biomarkers have been found, no good biomarkers have been found yet for anti-VEGF agents. Aflibercept and regorafenib have recently also been approved in patients with mCRC. This article reviews in an extensive way the data of large randomized clinical trials for the use of anti-VEGF and anti-EGFR in CRC. Aim of this review is also to describe the current status of biomarkers discovery and highlight how to improve the therapeutic index of these targeted agents by selecting in advance the subgroup of patients who will benefit from these treatments.
尽管结直肠癌（CRC）的发病率和死亡率有所下降，但它仍然是全球第二大常见癌症。手术后和辅助治疗后的复发以及转移性疾病仍然是一个主要问题，总生存期中位数约为 24 个月。然而，由于新的细胞毒性药物和靶向药物在临床实践中的应用，治疗效果得到了改善。改善 CRC 现有化疗方案疗效的靶向药物是针对血管内皮生长因子（VEGF）和表皮生长因子受体（EGFR）的药物。贝伐珠单抗是一种针对 VEGF 的重组人源化单克隆抗体，西妥昔单抗和帕尼单抗是两种针对 EGFR 的单克隆抗体，它们已被批准用于治疗转移性结直肠癌（mCRC）。虽然已经发现了针对抗 EGFR 药物的预测性生物标志物，但尚未发现针对抗 VEGF 药物的良好生物标志物。阿柏西普和瑞戈非尼最近也已被批准用于 mCRC 患者。本文全面回顾了抗 VEGF 和抗 EGFR 在 CRC 中的大型随机临床试验数据。本文的目的还在于描述生物标志物发现的现状，并强调如何通过预先选择将从这些治疗中受益的患者亚组来提高这些靶向药物的治疗指数。
