Bergmann Lothar, Maute Luise, Guschmann Michael
Medizinische Klinik II, J.W. Goethe Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany.
Expert Rev Anticancer Ther. 2014 Jan;14(1):9-21. doi: 10.1586/14737140.2014.864562. Epub 2013 Dec 6.
Renal cell carcinomas (RCCs) represent one of the ten leading cancer entities with an increasing incidence especially in the western world. Unfortunately, about 25% of the patients develop metastatic RCC (mRCC) associated with a most unfavorable prognosis. In the recent years, various new agents targeting VEGF or VEGF receptor (VEGFR) or the mTOR pathway have been approved for the treatment of mRCC with significant prolongation of progression-free survival and, in part, of overall survival (OS). Targeting the mTOR kinase is an interesting option for mRCC. Temsirolimus, one of the available mTOR inhibitors, has been approved as a single agent in poor-risk mRCC patients based on the pivotal Phase III trial showing a significant superiority in OS versus IFN-α or temsirolimus + IFN-α, which has been verified by a pivotal Phase III trial. The benefit has been shown for clear cell carcinoma and papillary RCC as well. For poor prognosis patients, temsirolimus improves median survival by 3.6 months. In second-line treatment compared with sorafenib following first-line treatment with sunitinib temsirolimus showed a relative progression-free survival benefit for patients with nonclear cell RCC with temsirolimus. The median OS for the temsirolimus group was 12.27 and 16.64 months for the sorafenib group. In 2007, the US FDA granted approval for temsirolimus for the treatment of advanced RCC.
肾细胞癌（RCC）是十大主要癌症类型之一，其发病率呈上升趋势，在西方世界尤为明显。不幸的是，约25%的患者会发展为转移性肾细胞癌（mRCC），预后极差。近年来，多种靶向血管内皮生长因子（VEGF）或VEGF受体（VEGFR）或雷帕霉素靶蛋白（mTOR）通路的新型药物已被批准用于治疗mRCC，可显著延长无进展生存期，部分还能延长总生存期（OS）。靶向mTOR激酶是治疗mRCC的一个有前景的选择。替西罗莫司是现有的mTOR抑制剂之一，基于关键的III期试验已被批准作为单一药物用于低危mRCC患者，该试验显示其在OS方面显著优于干扰素-α或替西罗莫司+干扰素-α，这一点已在关键的III期试验中得到验证。在透明细胞癌和乳头状RCC中也显示出了疗效。对于预后较差的患者，替西罗莫司可将中位生存期提高3.6个月。在一线使用舒尼替尼治疗后，二线使用替西罗莫司与索拉非尼相比，替西罗莫司对非透明细胞RCC患者显示出相对的无进展生存获益。替西罗莫司组的中位OS为12.27个月，索拉非尼组为16.64个月。2007年，美国食品药品监督管理局（FDA）批准替西罗莫司用于治疗晚期RCC。
