Herbst Roy S
Section of Thoracic Medical Oncology, Department of Thoraci/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030-4095, USA.
J Natl Compr Canc Netw. 2004 Sep;2 Suppl 2:S41-51.
Epidermal growth factor receptor expression has been shown to contribute to the growth and survival of tumor cells via several mechanisms. High levels of this expression are common in patients with non-small cell lung cancer and correlate with decreased survival. Two classes of epidermal growth factor receptor inhibitors are currently under investigation: tyrosine kinase inhibitors and monoclonal antibodies, including cetuximab. To date, results of phase II or III trials of tyrosine kinase inhibitors have yielded mixed results, with moderate activity but no increase in survival reported in patients with advanced non-small cell lung cancer. Recently reported results of phase II trials of cetuximab in combination with chemotherapy show the feasibility and activity of these combinations, with overall response rates of 22% to 53% in previously treated and untreated patients. The primary toxicity of epidermal growth factor receptor inhibitors is mild-to-moderate rash that is occasionally severe. In addition, hypersensitivity reactions are uncommonly reported with monoclonal antibodies, and orally administered tyrosine kinase inhibitors are associated with diarrhea that can be dose limiting. Combining epidermal growth factor receptor inhibitors with chemotherapy does not appear to increase chemotherapy-related toxicity. One tyrosine kinase inhibitor, ZD1839, has been associated with a low incidence of interstitial lung disease. Results to date suggest a potential role of epidermal growth factor receptor inhibition in non-small cell lung cancer, and investigation into the optimal use of these inhibitors continues.
表皮生长因子受体的表达已被证明可通过多种机制促进肿瘤细胞的生长和存活。这种高表达在非小细胞肺癌患者中很常见，且与生存率降低相关。目前正在研究两类表皮生长因子受体抑制剂：酪氨酸激酶抑制剂和单克隆抗体，包括西妥昔单抗。迄今为止，酪氨酸激酶抑制剂的II期或III期试验结果喜忧参半，晚期非小细胞肺癌患者的活性中等，但生存率未见提高。最近报道的西妥昔单抗联合化疗的II期试验结果显示了这些联合治疗的可行性和活性，既往接受过治疗和未接受过治疗的患者的总缓解率为22%至53%。表皮生长因子受体抑制剂的主要毒性是轻度至中度皮疹，偶尔会很严重。此外，单克隆抗体很少报告有过敏反应，口服酪氨酸激酶抑制剂会导致腹泻，这可能会限制剂量。将表皮生长因子受体抑制剂与化疗联合使用似乎不会增加化疗相关毒性。一种酪氨酸激酶抑制剂ZD1839与间质性肺病的低发病率有关。迄今为止的结果表明表皮生长因子受体抑制在非小细胞肺癌中具有潜在作用，对这些抑制剂的最佳使用的研究仍在继续。
