Beth Israel Deaconess Medical Center, Department of Medicine, Division of Hematology/Oncology, 375 Longwood Avenue, MS 428, Boston, MA 02215, USA.
Cancer Treat Rev. 2010 May;36(3):216-23. doi: 10.1016/j.ctrv.2009.12.003. Epub 2010 Jan 29.
The availability of molecularly targeted agents has improved outcomes for patients with renal cell carcinoma (RCC), a disease long considered refractory to systemic therapy. The hypervascularity observed in RCC tumors, which is driven by the inactivation of the vonHippel-Lindau gene, provided a rationale for targeting angiogenesis, in particular vascular endothelial growth factor (VEGF). Bevacizumab, a potent and specific anti-VEGF monoclonal antibody, has demonstrated significant clinical benefits when used in combination with interferon-alfa (IFN-alpha) for the treatment of metastatic RCC in two randomized phase III trials. The use of bevacizumab with IFN-alpha received approval in Europe for the first-line treatment of patients with advanced or metastatic RCC, and more recently this combination was approved for use in patients with mRCC in the United States. Bevacizumab with IFN-alpha has also been recommended by the National Comprehensive Cancer Network for first-line therapy of relapsed or metastatic unresectable RCC with predominantly clear cell histology. Two phase II studies suggest that bevacizumab has single-agent activity, which is characterized by encouraging progression-free survival rates and evidence of tumor regressions in patients with advanced or metastatic RCC. Here we review these trials along with recent and ongoing studies that explore the combination of bevacizumab with other targeted agents, its optimal sequencing with tyrosine kinase inhibitors, and its combination with low-dose IFN-alpha. Collectively, these studies allow the role of bevacizumab-based therapy to be defined in the context of a new and evolving algorithm for the treatment of patients with advanced RCC.
分子靶向药物的出现改善了肾细胞癌（RCC）患者的预后，这种疾病长期以来被认为对全身治疗具有抗性。RCC 肿瘤中观察到的血管过度生成是由 von Hippel-Lindau 基因失活驱动的，这为靶向血管生成提供了依据，特别是血管内皮生长因子（VEGF）。贝伐珠单抗是一种强效和特异性的抗 VEGF 单克隆抗体，在两项随机 III 期试验中与干扰素-α（IFN-α）联合用于转移性 RCC 的治疗时，显示出显著的临床益处。贝伐珠单抗联合 IFN-α在欧洲被批准用于晚期或转移性 RCC 患者的一线治疗，最近在美国，该联合方案也被批准用于 mRCC 患者。贝伐珠单抗联合 IFN-α也被美国国家综合癌症网络推荐用于一线治疗以透明细胞组织学为主的复发性或转移性不可切除的 RCC。两项 II 期研究表明，贝伐珠单抗具有单药活性，其特征是在晚期或转移性 RCC 患者中具有令人鼓舞的无进展生存率和肿瘤消退的证据。在此，我们回顾了这些试验以及最近正在进行的研究，这些研究探讨了贝伐珠单抗与其他靶向药物的联合应用、其与酪氨酸激酶抑制剂的最佳序贯应用以及与低剂量 IFN-α的联合应用。总的来说，这些研究使贝伐珠单抗治疗的作用在治疗晚期 RCC 的新的和不断发展的算法背景下得到了明确。
