Zhu Andrew X, Stuart Keith, Blaszkowsky Lawrence S, Muzikansky Alona, Reitberg Donald P, Clark Jeffrey W, Enzinger Peter C, Bhargava Pankaj, Meyerhardt Jeffrey A, Horgan Kerry, Fuchs Charles S, Ryan David P
Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA.
Cancer. 2007 Aug 1;110(3):581-9. doi: 10.1002/cncr.22829.
Epidermal growth factor receptor (EGFR) and ligand expression is frequently seen in hepatocellular carcinoma (HCC). A phase 2 study was performed with cetuximab, a chimeric monoclonal antibody that binds specifically to EGFR, in patients with advanced HCC.
Eligibility criteria included unresectable or metastatic measurable HCC, an Eastern Cooperative Oncology Group performance status <or=2, Cancer of the Liver Italian Program (CLIP) score <or=3, and adequate organ functions. The initial dose of cetuximab was 400 mg/m(2) given intravenously followed by weekly intravenous infusions at 250 mg/m(2). Each cycle was defined as 6 consecutive weekly treatments. EGFR expression was assayed by immunohistochemistry and trough serum concentrations of cetuximab were determined during the first cycle.
Thirty patients were enrolled and assessable for efficacy and toxicity. No responses were seen. Five patients had stable disease (median time, 4.2 months; range, 2.8-4.2 months). The median overall survival was 9.6 months (95% confidence interval [CI], 4.3-12.1 months) and the median progression-free survival (PFS) was 1.4 months (95% CI, 1.2-2.6 months). The treatment was generally well tolerated. No treatment-related grade 4-5 toxicities occurred. Grade 3 (according to the National Cancer Institute's Common Terminology Criteria for Adverse Events [version 3.0]) aspartate aminotransferase, hypomagnesemia, and fever without neutropenia were noted in 1 patient (3.3%) each. On Week 6 of Cycle 1, arithmetic mean serum cetuximab concentrations for patients with Child-Turcotte-Pugh (CTP) A and CTP B disease were 47.6 mcg/mL and 66.9 mcg/mL, respectively.
Although cetuximab could be safely administered with tolerable toxicity profiles, it demonstrated no antitumor activity in HCC in this phase 2 study. Cetuximab trough concentrations were not notably altered in patients with mild to moderate hepatic dysfunction.
表皮生长因子受体（EGFR）及其配体的表达在肝细胞癌（HCC）中较为常见。一项2期研究对西妥昔单抗（一种特异性结合EGFR的嵌合单克隆抗体）用于晚期HCC患者进行了评估。
入选标准包括无法切除或转移性可测量的HCC、东部肿瘤协作组（Eastern Cooperative Oncology Group）体能状态≤2、意大利肝癌项目（Cancer of the Liver Italian Program，CLIP）评分≤3以及器官功能良好。西妥昔单抗的初始剂量为400mg/m²静脉注射，随后每周静脉输注250mg/m²。每个周期定义为连续6周的治疗。通过免疫组织化学检测EGFR表达，并在第1周期测定西妥昔单抗的谷血清浓度。
30例患者入组并可评估疗效和毒性。未观察到缓解病例。5例患者病情稳定（中位时间4.2个月；范围2.8 - 4.2个月）。中位总生存期为9.6个月（95%置信区间[CI]，4.3 - 12.1个月），中位无进展生存期（PFS）为1.4个月（95%CI，1.2 - 2.6个月）。该治疗总体耐受性良好。未发生与治疗相关的4 - 5级毒性反应。1例患者（3.3%）出现3级（根据美国国立癌症研究所不良事件通用术语标准[第3.0版]）天冬氨酸转氨酶升高、低镁血症和无中性粒细胞减少的发热。在第1周期第6周，Child - Turcotte - Pugh（CTP）A和CTP B疾病患者的西妥昔单抗算术平均血清浓度分别为47.6μg/mL和66.9μg/mL。
尽管西妥昔单抗可以安全给药且毒性可耐受，但在这项2期研究中其在HCC中未显示出抗肿瘤活性。轻度至中度肝功能不全患者的西妥昔单抗谷浓度无明显改变。
