Department of Medicine, Royal Marsden Hospital, London SW3 6JJ, UK.
Ther Adv Med Oncol. 2009 Jul;1(1):15-27. doi: 10.1177/1758834009338430.
Renal cell carcinoma (RCC) accounts for approximately 3% of all cancers and is refractory to cytotoxic chemotherapy - immunotherapy has until recently been the standard of care for advanced disease. Randomised trials reported in the last 5 years have demonstrated that a number of agents including the monoclonal antibody, bevacizumab, and the kinase inhibitors - sorafenib sunitinib, temsirolimus and everolimus - are active in advanced RCC. Bevacizumab is directed against the vascular endothelial growth factor (VEGF), a key mediator of angiogenesis, whilst sorafenib and sunitinib inhibit a number of targets including the VEGF and platelet-derived growth factor (PDGFR) receptor tyrosine kinases. Temsirolimus and everolimus inhibit the intracellular mammalian target of rapamycin (mTOR) kinase. Sunitinib and temsirolimus have demonstrated efficacy in comparison with immunotherapy in the first-line setting in patients with favourable and poor prognosis advanced disease respectively. In the second-line setting, everolimus has shown benefit over placebo in patients who progress following treatment with a VEGF receptor tyrosine kinase inhibitor and sorafenib has demonstrated efficacy in comparison with placebo in patients with immunotherapy-refractory disease. We review here recent clinical trial data and discuss future developments in the systemic treatment of RCC including combination and sequential therapy, adjuvant therapy, the role of biomarkers and the prospects for the development of rational mechanism-directed therapy in this disease.
肾细胞癌 (RCC) 约占所有癌症的 3%,对细胞毒性化疗具有抗性 - 免疫疗法直到最近一直是晚期疾病的标准治疗方法。过去 5 年报告的随机试验表明,包括单克隆抗体贝伐珠单抗和激酶抑制剂索拉非尼、舒尼替尼、替西罗莫司和依维莫司在内的多种药物在晚期 RCC 中具有活性。贝伐珠单抗针对血管内皮生长因子 (VEGF),这是血管生成的关键介质,而索拉非尼和舒尼替尼抑制包括 VEGF 和血小板衍生生长因子 (PDGFR) 受体酪氨酸激酶在内的多个靶点。替西罗莫司和依维莫司抑制细胞内哺乳动物雷帕霉素靶蛋白 (mTOR) 激酶。舒尼替尼和替西罗莫司在一线治疗中与免疫疗法相比,在预后良好和预后不良的晚期疾病患者中均显示出疗效。在二线治疗中,依维莫司在接受 VEGF 受体酪氨酸激酶抑制剂治疗后进展的患者中显示出优于安慰剂的益处,索拉非尼在免疫疗法难治性疾病患者中与安慰剂相比显示出疗效。我们在此回顾了最近的临床试验数据,并讨论了 RCC 系统治疗的未来发展,包括联合和序贯治疗、辅助治疗、生物标志物的作用以及在这种疾病中开发合理的机制导向治疗的前景。