Department of Medical Oncology, University of Groningen, University Medical Center Groningen, The Netherlands.
Crit Rev Oncol Hematol. 2012 Nov;84(2):224-42. doi: 10.1016/j.critrevonc.2012.03.006. Epub 2012 Apr 21.
Despite efforts to improve chemotherapeutic efficacy in epithelial ovarian cancer, outcome for patients with advanced disease has remained unchanged since the introduction of standard carboplatin and paclitaxel. Interest has therefore shifted toward molecularly targeted therapies that interfere with important features of ovarian carcinogenesis, such as angiogenesis. Several angiogenesis inhibitors, targeting vascular endothelial growth factor (VEGF) ligands (bevacizumab, VEGF-Trap) or their receptors (VEGFR-targeted tyrosine kinase inhibitors) have been clinically evaluated. These agents demonstrated efficacy in phase II clinical trials. Results from phase III trials, in which bevacizumab was added to standard frontline chemotherapy, show a modest effect. Although the initial expectations for angiogenesis inhibitors have been tempered, further research is warranted to define their precise place in the treatment of ovarian cancer. This review summarizes the performed and ongoing studies with regard to angiogenesis inhibitors in ovarian cancer, and the available data on biomarkers for response prediction. Preclinical studies evaluating alternative angiogenesis inhibitors will also be discussed.
尽管在提高上皮性卵巢癌的化疗疗效方面做出了努力,但自从标准卡铂和紫杉醇问世以来,晚期疾病患者的预后仍未改变。因此,人们的兴趣转向了针对卵巢癌发生的重要特征(如血管生成)的分子靶向治疗。已经对几种针对血管内皮生长因子 (VEGF) 配体(贝伐珠单抗、VEGF 陷阱)或其受体(VEGFR 靶向酪氨酸激酶抑制剂)的血管生成抑制剂进行了临床评估。这些药物在 II 期临床试验中显示出疗效。在将贝伐珠单抗添加到标准一线化疗中进行的 III 期试验的结果表明,其疗效较为温和。尽管对血管生成抑制剂的最初期望已经降低,但仍需要进一步的研究来确定它们在卵巢癌治疗中的确切位置。这篇综述总结了关于卵巢癌中血管生成抑制剂的已完成和正在进行的研究,以及关于反应预测的生物标志物的现有数据。还将讨论评估替代血管生成抑制剂的临床前研究。