转移性肾癌靶向治疗现状与进展剖析.ppt

最常见的不良反应为： 腹泻 [55%] 高血压 [40%] 乏力 [39%] 厌食[34%] 恶心[32%] 这些不良反应大部分仅轻到中度 因此，阿昔替尼被NCCN委员会作为1类证据推荐用于晚期肾癌的二线治疗。 阿昔替尼对比索拉非尼一线治疗转移性肾癌的Ⅲ期临床研究 国际多中心III期临床试验结果： 舒尼替尼客观缓解率为47%，中位PFS为11个月，中位OS为26.4个月，均优于对照组干扰素治疗 Motzer RJ,?et al. N Engl J Med.?2007 Motzer RJ,?et al. J Clin Oncol.?2009 舒尼替尼的疗效数据仍未被超越 八九十年代，细胞因子曾是晚期肾癌的标准治疗，但有效率为10-15％，且生存获益有限。2006年FDA正式批准索拉非尼和舒尼替尼用于治疗晚期肾癌，从此晚期肾癌的治疗进入分子靶向治疗时代。到目前为止，美国食品药品管理局(FDA)批准的可用于治疗mRCC的分子靶向药物主要有7种：索拉非尼、舒尼替尼、贝伐单抗、替西罗莫司、依维莫司、帕唑帕尼和阿昔替尼。国内上市的药物有4种：索拉非尼、舒尼替尼、依维莫司和阿昔替尼。 * * 1. Rini BI, Small EJ. Biology and clinical development of vascular endothelial growth factor–targeted therapy in renal cell carcinoma. J Clin Oncol. 2005;23:1028-1043. 2. Duensing A, Heinrich MC, Fletcher CDM, Fletcher JA. Biology of gastrointestinal stromal tumors: KIT mutations and beyond. Cancer Invest. 2004;22:106-116. 3. Marmor MD, Skaria KB, Yarden Y. Signal transduction and oncogenesis by ErbB/HER receptors. Int J Radiat Oncol Biol Phys. 2004;58:903-913. 4. Tibes R, Trent J, Kurzrock R. Tyrosine kinase inhibitors and the dawn of molecular cancer therapeutics. Annu Rev Pharmacol Toxicol. 2005;45:357-384. 5. Corless CL, Fletcher JA, Heinrich MC. Biology of gastrointestinal tumors. J Clin Oncol. 2004;22:3813-3825. 6. Bergers G, Song S. The role of pericytes in blood-vessel formation and maintenance. Neuro-Oncology. 2005;7:452-464. References * (Treatment Approaches in Renal Cancer Global Evaluation Trial ) phase 3, randomized, double-blind, placebo-controlled trial continuous treatment with oral sorafenib (at a dose of 400 mg twice daily) or placebo in a double-blind fashion * Figure 2. Kaplan–Meier Analysis of Overall Survival and Progression-free Survival. Panel A shows the probability of overall survival among 903 patients — 451 receiving sorafenib and 452 receiving placebo — in May 2005, when patients receiving placebo were allowed to switch to sorafenib (P = 0.02 for the comparison between the two study groups; O’Brien–Fleming threshold for statistical s