Zhang Wu, Gordon Michael, Lenz Heinz-Josef
Division of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, California 90033, USA.
Ann Med. 2006;38(8):545-51. doi: 10.1080/09546630601070812.
The standard treatment of metastatic colorectal cancer (mCRC) is combination of 5- fluorouracil/folinic acid with irinotecan or oxaliplatin-based chemotherapy. Epidermal growth factor receptor (EGFR) is overexpressed in 70%-80% of colorectal cancers (CRC). EGFR overexpression is known to be involved in carcinogenic processes, such as cell proliferation, apoptosis, angiogenesis and metastasis. Monoclonal antibodies targeting EGFR have shown antitumor activity and improved the efficacy of chemotherapy. Cetuximab is a chimeric immunoglobulin (Ig) G1 anti-EGFR monoclonal antibody (MoAb). Several clinical studies have shown cetuximab, either as a single agent or in combination with irinotecan, having promising efficacy in patients with metastatic CRC. Cetuximab with 5-fluorouracil/LV (leucovorin) plus irinotecan or oxaliplatin-based chemotherapy has shown higher response rate and longer time to progression as first-line treatment of mCRC. Currently, there are no data showing that addition of cetuximab would prolong overall survival in randomized studies. Panitumumab, a fully human IgG2 monoclonal antibody, has also shown antitumor activity against EGFR-expressing mCRC with less allergic reaction. Anti-EGFR MoAbs are well tolerated and have limited overlapping toxicities in combination with other cytotoxic drugs. The most common side effect of anti-EGFR MoAb is an acneform skin rash, which is a surrogate marker of efficacy of treatment with MoAbs. In this review, we will discuss the use of anti-EGFR MoAbs in the treatment of mCRC, with focus on cetuximab and panitumumab.
转移性结直肠癌（mCRC）的标准治疗方法是将5-氟尿嘧啶/亚叶酸与伊立替康或奥沙利铂为基础的化疗联合使用。表皮生长因子受体（EGFR）在70%-80%的结直肠癌（CRC）中过度表达。已知EGFR过度表达参与致癌过程，如细胞增殖、凋亡、血管生成和转移。靶向EGFR的单克隆抗体已显示出抗肿瘤活性并提高了化疗疗效。西妥昔单抗是一种嵌合免疫球蛋白（Ig）G1抗EGFR单克隆抗体（MoAb）。多项临床研究表明，西妥昔单抗作为单一药物或与伊立替康联合使用，对转移性CRC患者具有有前景的疗效。西妥昔单抗与5-氟尿嘧啶/亚叶酸（甲酰四氢叶酸）加伊立替康或奥沙利铂为基础的化疗联合使用，作为mCRC的一线治疗，已显示出更高的缓解率和更长的疾病进展时间。目前，在随机研究中没有数据表明添加西妥昔单抗会延长总生存期。帕尼单抗是一种完全人源化的IgG2单克隆抗体，也显示出对表达EGFR的mCRC具有抗肿瘤活性且过敏反应较少。抗EGFR MoAbs耐受性良好，与其他细胞毒性药物联合使用时毒性重叠有限。抗EGFR MoAb最常见的副作用是痤疮样皮疹，这是MoAbs治疗疗效的替代标志物。在本综述中，我们将讨论抗EGFR MoAbs在mCRC治疗中的应用，重点是西妥昔单抗和帕尼单抗。
