Department of Medicine, Royal Marsden Hospital, London, SW3 6JJ, United Kingdom.
Oncologist. 2009 Dec;14(12):1218-24. doi: 10.1634/theoncologist.2009-0105. Epub 2009 Nov 25.
Outcomes for patients with advanced renal cell carcinoma (RCC) have improved significantly in recent years with the development of novel noncytotoxic systemic therapies. The multitargeted kinase inhibitors sunitinib and sorafenib have been approved for the treatment of advanced RCC, and bevacizumab, a monoclonal anti-vascular endothelial growth factor antibody, has shown significant clinical activity, both as a single agent and in combination with interferon-alpha. The mammalian target of rapamycin inhibitors temsirolimus and everolimus have led to longer overall survival times in poor-risk patients in the first-line setting and longer progression-free survival times in kinase inhibitor refractory patients in the second-line setting, respectively. Despite these advances, almost all patients develop resistance to treatment and cure is rarely seen. There is therefore a need to overcome resistance, induce longer lasting remissions, and improve survival. A potential approach to this is to combine active agents, and the clinical data for combination therapy with novel targeted agents in advanced RCC are reviewed here.
近年来，随着新型非细胞毒性全身治疗方法的发展，晚期肾细胞癌 (RCC) 患者的治疗效果显著改善。多靶点激酶抑制剂舒尼替尼和索拉非尼已被批准用于治疗晚期 RCC，而贝伐单抗作为一种单克隆抗血管内皮生长因子抗体，无论是作为单一药物还是与干扰素-α联合使用，均显示出显著的临床活性。哺乳动物雷帕霉素靶蛋白抑制剂替西罗莫司和依维莫司分别导致一线治疗中高危风险患者的总生存期延长和二线治疗中激酶抑制剂耐药患者的无进展生存期延长。尽管取得了这些进展，但几乎所有患者最终都会对治疗产生耐药性，很少有患者能被治愈。因此，需要克服耐药性，诱导更持久的缓解，并改善生存。一种潜在的方法是联合应用活性药物，本文综述了晚期 RCC 中新型靶向药物联合治疗的临床数据。
