Hirsch Fred R, Witta Samir
University of Colorado Cancer Center, Department of Medicine/Medical Oncology and Pathology, Aurora, Colorado 80010, USA.
Curr Opin Oncol. 2005 Mar;17(2):118-22. doi: 10.1097/01.cco.0000155059.39733.9d.
Epidermal growth factor receptor (EGFR) Inhibitors have shown promising results in patients with advanced non-small cell lung cancers (NSCLC) who previously have failed on chemotherapy. Objective response is achieved in 10 to 28% of the patients, and about 30% will achieve stable disease. A major problem is how to select the patients, who will benefit from treatment, and who will not.
The predictive role of EGFR protein expression assessed by IHC is still debated. Specific EGFR gene mutations have been identified associated with response to gefitinib (Iressa(R)), but seem not to be associated with stable disease. No studies have yet demonstrated any association between EGFR gene mutations and survival. In this review we describe other marker studies, which are associated with sensitivity to EGFR inhibitors. Increased EGFR gene copy number based on FISH analysis is demonstrated to be a good predictive marker for response, stable disease, time to progression, and survival.
EGFR/FISH seems today to be the best predictive marker for clinical benefit from EGFR inhibitors in NSCLC. Prospective large scale clinical studies must identify the most optimal paradigm for selection of patients.
表皮生长因子受体（EGFR）抑制剂在既往化疗失败的晚期非小细胞肺癌（NSCLC）患者中显示出了有前景的结果。10%至28%的患者可获得客观缓解，约30%的患者病情稳定。一个主要问题是如何选择能从治疗中获益的患者以及不能获益的患者。
通过免疫组化（IHC）评估的EGFR蛋白表达的预测作用仍存在争议。已确定特定的EGFR基因突变与吉非替尼（易瑞沙®）的反应相关，但似乎与病情稳定无关。尚无研究证明EGFR基因突变与生存之间存在任何关联。在本综述中，我们描述了其他与EGFR抑制剂敏感性相关的标志物研究。基于荧光原位杂交（FISH）分析的EGFR基因拷贝数增加被证明是反应、病情稳定、进展时间和生存的良好预测标志物。
如今，EGFR/FISH似乎是NSCLC患者从EGFR抑制剂中获得临床获益的最佳预测标志物。前瞻性大规模临床研究必须确定选择患者的最优模式。
