Giaccone Giuseppe
Department of Medical Oncology, VU University Medical Center, Amsterdam, the Netherlands.
Clin Cancer Res. 2007 Apr 1;13(7):1961-70. doi: 10.1158/1078-0432.CCR-06-2186.
The long-term prognosis for patients with advanced non-small cell lung cancer (NSCLC) remains poor despite the availability of several cytotoxic chemotherapy regimens. The use of targeted therapies, particularly those against the key mediator of angiogenesis vascular endothelial growth factor (VEGF), has the potential to improve outcomes for NSCLC patients. Bevacizumab, a recombinant humanized monoclonal anti-VEGF antibody, is the most clinically advanced antiangiogenic agent in NSCLC. In a phase III study, bevacizumab showed significantly improved overall and progression-free survival when used in combination with standard first-line chemotherapy in patients with advanced NSCLC. Bevacizumab was generally well tolerated in patients with NSCLC; however, tumor-related bleeding adverse events have been noted in some patients, predominantly those with squamous cell histology or centrally located tumors. Several small-molecule VEGF receptor tyrosine kinase inhibitors have also shown promise in phase I and II trials in NSCLC. This review summarizes the most important findings of angiogenesis inhibitors in NSCLC and discusses the potential for the use of these novel agents in different settings of NSCLC.
尽管有几种细胞毒性化疗方案可供使用，但晚期非小细胞肺癌（NSCLC）患者的长期预后仍然很差。使用靶向治疗，特别是那些针对血管生成关键介质血管内皮生长因子（VEGF）的治疗，有可能改善NSCLC患者的治疗结果。贝伐单抗是一种重组人源化抗VEGF单克隆抗体，是NSCLC中临床上最先进的抗血管生成药物。在一项III期研究中，贝伐单抗与晚期NSCLC患者的标准一线化疗联合使用时，显示出总体生存期和无进展生存期显著改善。贝伐单抗在NSCLC患者中总体耐受性良好；然而，在一些患者中已注意到与肿瘤相关的出血不良事件，主要是那些具有鳞状细胞组织学或中央型肿瘤的患者。几种小分子VEGF受体酪氨酸激酶抑制剂在NSCLC的I期和II期试验中也显示出前景。本综述总结了NSCLC中血管生成抑制剂的最重要发现，并讨论了在NSCLC不同情况下使用这些新型药物的潜力。
