Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Cancer Manag Res. 2010 Mar 9;2:61-70.
With the increasing understanding of the biology of the disease and the development of targeted therapy, there has been a paradigm shift in the treatment of clear cell metastatic renal cell carcinoma (mRCC). Traditionally patients with metastatic RCC have been treated with immunotherapy which has limited efficacy. The multikinase inhibitors sunitinib, sorafenib and pazopanib, the VEGF antibody bevacizumab in combination with interferon and the mTOR inhibitor temsirolimus have all been shown to prolong progression-free survival in phase III studies. Here we review another mTOR inhibitor, everolimus (Afinitor(®); Novartis, USA) which was approved in March 2009 by the US FDA for treatment of targeted-therapy refractory metastatic renal cell cancer. The phase III study of everolimus (the RECORD study) was terminated early after a significant difference in efficacy was noted in the treatment arm with everolimus (progression-free survival of 4.0 months in patients on the treatment arm vs 1.9 months in the placebo arm). The most common adverse events were stomatitis, pneumonitis, fatigue and infections. We review Phase I-III data with a particular emphasis on safety data and patient focused outcomes.
随着对疾病生物学的认识不断加深和靶向治疗的发展，透明细胞转移性肾细胞癌 (mRCC) 的治疗已经发生了范式转变。传统上，转移性 RCC 患者接受免疫治疗，但其疗效有限。多激酶抑制剂舒尼替尼、索拉非尼和帕唑帕尼、VEGF 抗体贝伐珠单抗联合干扰素和 mTOR 抑制剂替西罗莫司在 III 期研究中均已证明可延长无进展生存期。在这里，我们回顾另一种 mTOR 抑制剂依维莫司（Afinitor®；诺华制药，美国），该药于 2009 年 3 月获得美国 FDA 批准用于治疗靶向治疗耐药转移性肾细胞癌。依维莫司的 III 期研究（RECORD 研究）在治疗组中观察到疗效显著差异后提前终止，依维莫司治疗组的无进展生存期为 4.0 个月，安慰剂组为 1.9 个月。最常见的不良反应是口腔炎、肺炎、疲劳和感染。我们回顾了 I-III 期的数据，特别强调了安全性数据和以患者为中心的结果。
