Fakih Marwan
From the City of Hope Comprehensive Cancer Center, Duarte, CA.
Am Soc Clin Oncol Educ Book. 2015:e197-206. doi: 10.14694/EdBook_AM.2015.35.e197.
The role of antiangiogenic and anti-epidermal growth factor receptor (EGFR) agents has been investigated extensively in colorectal cancer in the palliative, adjuvant, and neoadjuvant settings. Although the role of biologic agents has become well-defined in the first, second, and subsequent lines of treatment of metastatic colorectal cancer (mCRC), considerable debate continues around the optimal sequencing and around optimal patient selection. The benefits from integrating bevacizumab or cetuximab in the adjuvant setting have been investigated in several randomized phase III clinical trials in stage II/III disease, all with disappointing results. Neoadjuvant approaches incorporating biologic therapy in patients with liver metastatic disease have led to mixed results. Although the current evidence does suggest increased down-staging and increased resectability with the addition of cetuximab in patients with initially unresectable or borderline resectable liver metastases, a positive effect of anti-EGFR therapy on the overall survival (OS) in this setting is not conclusive. Patients with resectable liver metastases derive no benefit and may experience potential harm from the addition of cetuximab to neoadjuvant chemotherapy. Similarly, there is neither rationale nor adequate data to support the addition of bevacizumab to neoadjuvant chemotherapy in patients with resectable liver metastases. In this review, we examine the role of antiangiogenesis and anti-EGFR therapies across the spectrum of adjuvant, neoadjuvant, and metastatic disease.
抗血管生成和抗表皮生长因子受体（EGFR）药物在结直肠癌的姑息、辅助和新辅助治疗中的作用已得到广泛研究。尽管生物制剂在转移性结直肠癌（mCRC）的一线、二线及后续治疗中的作用已明确，但围绕最佳治疗顺序和最佳患者选择仍存在大量争议。在II/III期疾病的多项随机III期临床试验中，对在辅助治疗中联合使用贝伐单抗或西妥昔单抗的益处进行了研究，结果均令人失望。在肝转移疾病患者中采用生物治疗的新辅助治疗方法，结果喜忧参半。尽管目前的证据确实表明，在最初不可切除或边缘可切除的肝转移患者中，加用西妥昔单抗可增加降期并提高可切除性，但在这种情况下抗EGFR治疗对总生存期（OS）的积极作用尚无定论。可切除肝转移患者无法从新辅助化疗中加用西妥昔单抗中获益，甚至可能受到潜在伤害。同样，也没有理由和充分的数据支持在可切除肝转移患者的新辅助化疗中加用贝伐单抗。在本综述中，我们探讨了抗血管生成和抗EGFR治疗在辅助、新辅助和转移性疾病中的作用。
