D'Andrea M R, Gasparini G
Division of Medical Oncology, Azienda Complesso Ospedaliero S. Filippo Neri, Rome - Italy.
Int J Biol Markers. 2007;22(4):88-93. doi: 10.1177/17246008070221s411.
We report here on the state of our knowledge of the target namely, the epidermal growth factor (EGF) and its receptor and the challenges related to the methods of determination of the epidermal growth factor receptor (EGFR) and associated molecular pathways. A critical review of the anti-EGFR therapeutic strategies is also outlined. The chimeric anti- EGFR monoclonal antibody cetuximab has been approved for EGFR-expressing colorectal tumors in patients who progress after irinotecan-based chemotherapy in combination with irinotecan and in squamous cell head and neck carcinomas for patients with locally advanced disease in combination with radiation therapy or after failure of platinum-based chemotherapy in recurrent or metastatic disease (FDA). Cetuximab has the potential to provide an improvement of clinical outcome also in other indications and tumor types, particularly when used as first-line therapy combined with standard chemotherapy for metastatic disease or in the adjuvant setting. Possible strategies to improve the effectiveness of anti-EGFR agents are suggested and include (i) the use of predictive tools capable of making a more rational selection of patients; (ii) the development of standardized predictive biomarkers as surrogates for early monitoring of drug efficacy; and (iii) adequate study design, statistical analysis and proper end points of efficacy to be applied in future prospective trials.
我们在此报告我们对靶点，即表皮生长因子（EGF）及其受体的了解现状，以及与表皮生长因子受体（EGFR）测定方法和相关分子途径有关的挑战。还概述了对EGFR靶向治疗策略的批判性综述。嵌合抗EGFR单克隆抗体西妥昔单抗已被批准用于接受过基于伊立替康的化疗联合伊立替康后病情进展的EGFR表达型结直肠癌患者，以及局部晚期疾病患者联合放疗或铂类化疗失败的复发或转移性疾病的鳞状细胞头颈癌患者（美国食品药品监督管理局）。西妥昔单抗也有可能在其他适应症和肿瘤类型中改善临床结局，特别是当作为一线治疗与转移性疾病的标准化疗联合使用或用于辅助治疗时。文中提出了提高抗EGFR药物有效性的可能策略，包括：（i）使用能够更合理选择患者的预测工具；（ii）开发标准化的预测生物标志物作为早期监测药物疗效的替代指标；以及（iii）在未来的前瞻性试验中应用适当的研究设计、统计分析和合适的疗效终点。
