Cetuximab - In the treatment of metastatic colorectal cancer
Cetuximab - In the treatment of metastatic colorectal cancer
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DOI：
10.2165/00003495-200464010-00007
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发表时间：
2004-01-01
期刊：
影响因子：
11.5
通讯作者：
Wagstaff, AJ
中科院分区：
文献类型：
--
作者：
Reynolds, NA;Wagstaff, AJ
西妥昔单抗是一种对表皮生长因子受体 (EGFR) 具有高度选择性的嵌合单克隆抗体，EGFR 在 25-80% 的结直肠癌肿瘤中过度表达，并与晚期疾病相关。西妥昔单抗在表达 EGFR 的肿瘤中诱导广泛的细胞反应，增强对放疗和化疗药物的敏感性。在一项针对伊立替康难治性、转移性成人患者的大型、随机、开放标签、多中心研究中表达 EGFR 的结直肠癌，与西妥昔单抗单药治疗相比，西妥昔单抗 400 mg/m2 初始剂量，随后每周 250 mg/m2 加伊立替康（各种剂量）可产生更高的部分缓解率和疾病控制率（部分缓解加稳定疾病），并延长疾病进展时间；两组的生存率相似。在三项小型开放标签试验中，相同剂量的西妥昔单抗联合伊立替康、氟尿嘧啶和亚叶酸（各种方案）使 43-58% 的患者产生部分缓解，5% 的患者获得完全缓解（仅一项研究），并且在 32-52% 的表达 EGFR 的初治转移性结直肠癌患者中，32-52% 的患者病情稳定。最常见的 3/4 级不良事件与西妥昔单抗单药治疗出现痤疮样皮疹、乏力、腹痛和恶心/呕吐。在接受西妥昔单抗联合伊立替康治疗的患者中，出现腹泻、乏力、白细胞减少和中性粒细胞减少的症状。
Cetuximab is a chimeric monoclonal antibody highly selective for the epidermal growth factor receptor (EGFR), which is over-expressed by 25-80% of colorectal cancer tumours and associated with advanced disease.Cetuximab induces a broad range of cellular responses in tumours expressing EGFR, enhancing sensitivity to radiotherapy and chemotherapeutic agents.In a large, randomised, open-label, multicentre study in adult patients with irinotecan-refractory, metastatic colorectal cancer expressing EGFR, cetuximab 400 mg/m(2) initial dose followed by 250 mg/m2 weekly plus irinotecan (various doses) produced a greater rate of partial response and disease control (partial response plus stable disease), and increased time to disease progression, compared with cetuximab monotherapy; survival was similar in both groups.The same dosage of cetuximab combined with irinotecan, fluorouracil and folinic acid (various regimens) produced partial responses in 43-58% of patients, a complete response in 5% of patients (one study only) and stable disease in 32-52% of patients with treatment-naive metastatic colorectal cancer expressing EGFR in three small, open-label trials.The most common grade 3/4 adverse events associated with cetuximab monotherapy were acne-like rash, asthenia, abdominal pain and nausea/vomiting. In patients receiving cetuximab plus irinotecan, these were diarrhoea, asthenia, leucopenia and neutropenia.