Langer Corey J
Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Expert Rev Anticancer Ther. 2003 Aug;3(4):443-55. doi: 10.1586/14737140.3.4.443.
New cytotoxic therapies, including the taxanes, gemcitabine (Gemzar), vinorelbine (Navelbine) and irinotecan (Campto), have improved treatment outcome and expanded treatment options in advanced non-small cell lung cancer. However, despite their promise, a therapeutic plateau with response rates of 20-30% and 1-year survival rates of 30-40% has been reached. It is doubtful if exchanging one agent for another in various combinations will lead to any significant improvement. The thrust of current research focuses on targeted therapy and its careful integration into the standard treatment paradigm. These agents include compunds targeted at growth factor receptors, angiogenesis, cyclooxygenase, farnesyl transferase and protein kinase C-alpha. Preclinical models have demonstrated synergy for many of these agents in combination with either chemotherapy or radiation, although clinical challenges exist. These include the identification of an optimal biologic dose, the proper integration of these agents into systemic chemotherapy regimens, and selecting the best setting in which to test the compounds.
包括紫杉烷类、吉西他滨（健择）、长春瑞滨（诺维本）和伊立替康（开普拓）在内的新型细胞毒性疗法，已改善了晚期非小细胞肺癌的治疗效果并拓展了治疗选择。然而，尽管它们前景广阔，但目前已达到了一个治疗平台期，缓解率为20%至30%，1年生存率为30%至40%。在各种联合方案中用一种药物替换另一种药物是否会带来显著改善，这一点值得怀疑。当前研究的重点在于靶向治疗及其与标准治疗模式的审慎整合。这些药物包括针对生长因子受体、血管生成、环氧化酶、法尼基转移酶和蛋白激酶C-α的化合物。临床前模型已证明，其中许多药物与化疗或放疗联合使用具有协同作用，尽管存在临床挑战。这些挑战包括确定最佳生物剂量、将这些药物合理整合到全身化疗方案中，以及选择测试这些化合物的最佳环境。
