Department of Medical Oncology, Institut de Cancérologie de la Loire, St-Priest en Jarez, France.
Clin Genitourin Cancer. 2012 Sep;10(3):147-52. doi: 10.1016/j.clgc.2012.05.002. Epub 2012 Jul 15.
Increased understanding of the molecular pathophysiology of metastatic renal cell carcinoma (mRCC) has led to development of antiangiogenic therapies in the past 5 years that significantly improved the prognosis. Vascular endothelial growth factor (VEGF) is a major growth factor in tumor angiogenesis and is implicated in tumor progression of several types of cancer, including mRCC. Use of 2 distinct approaches resulted in clinical efficacy in blocking the VEGF pathway: small molecule tyrosine kinase inhibitors (sunitinib, sorafenib, axitinib, pazopanib) and the humanized anti-VEGF monoclonal antibody bevacizumab that binds circulating VEGF and prevents activation of the VEGF receptor. In the 2 large phase III trials AVOREN and CALGB 90206, bevacizumab combined with interferon alfa demonstrated its efficacy as a first-line therapy in terms of progression-free survival. Nevertheless, in the era of targeted therapies, other studies are still needed to better obtain the maximal clinical benefit of bevacizumab. The aim of this overview is to report the current role of bevacizumab in the treatment of metastatic kidney cancer and to highlight possible combinations or sequential strategies that involve other targeted agents.
对转移性肾细胞癌（mRCC）分子病理生理学的认识不断提高，导致过去 5 年中开发了抗血管生成疗法，显著改善了预后。血管内皮生长因子（VEGF）是肿瘤血管生成的主要生长因子，与包括 mRCC 在内的多种癌症的肿瘤进展有关。使用 2 种不同的方法阻断 VEGF 途径取得了临床疗效：小分子酪氨酸激酶抑制剂（舒尼替尼、索拉非尼、阿昔替尼、帕唑帕尼）和人源化抗 VEGF 单克隆抗体贝伐珠单抗，后者可结合循环 VEGF 并阻止 VEGF 受体的激活。在两项大型 III 期试验 AVOREN 和 CALGB 90206 中，贝伐珠单抗联合干扰素-α在无进展生存期方面显示出作为一线治疗的疗效。然而，在靶向治疗时代，仍需要进行其他研究以更好地获得贝伐珠单抗的最大临床获益。本文旨在报告贝伐珠单抗在转移性肾癌治疗中的当前作用，并强调可能涉及其他靶向药物的联合或序贯策略。
