Department of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute, 9500 Euclid Avenue/Desk R35, Cleveland, OH 44195, USA.
Invest New Drugs. 2012 Feb;30(1):364-7. doi: 10.1007/s10637-010-9516-1. Epub 2010 Aug 14.
Therapies which target VEGF and mTOR are now available for patients with metastatic renal cell carcinoma, but there is a continued need to develop agents for patients who become refractory to these initial agents. Tandutinib is a relatively selective inhibitor of type III tyrosine kinase receptor kinases with promising activity in some tumors. In this trial, 10 patients with metastatic renal cell carcinoma refractory to previous therapy with sunitinib or sorafenib (median age 61 years, 80% performance status 0, 60% intermediate MSKCC risk classification) received tandutinib 500 mg bid daily with RECIST-defined response as the primary endpoint and progression-free survival (PFS) and overall survival (OS) as secondary endpoints. No patient had more than 2 cycles of therapy and 50% of patients only received 1 cycle with 70% of patients discontinuing for progressive disease and 30% for toxicity. Tandutinib was not well tolerated with dose reduction in 60% of patients due to adverse events. The most common grade 3 toxicity was fatigue (30%). Tandutinib had no clinical activity and due to the excessive toxicity should not be developed further in patients with sunitinib or sorafenib-refractory metastatic renal cell carcinoma.
针对血管内皮生长因子（VEGF）和哺乳动物雷帕霉素靶蛋白（mTOR）的治疗方法现已可用于转移性肾细胞癌患者，但仍需要为对这些初始药物产生耐药的患者开发新的药物。坦度替尼是一种相对选择性的 III 型酪氨酸激酶受体激酶抑制剂，在一些肿瘤中具有良好的活性。在这项试验中，10 名先前接受舒尼替尼或索拉非尼治疗（中位年龄 61 岁，80%表现状态 0，60%中间 MSKCC 风险分类）的转移性肾细胞癌患者对坦度替尼 500mg bid 每日治疗产生耐药，RECIST 定义的反应为主要终点，无进展生存期（PFS）和总生存期（OS）为次要终点。没有患者接受超过 2 个周期的治疗，50%的患者仅接受了 1 个周期，70%的患者因疾病进展而停药，30%的患者因毒性而停药。由于不良事件，坦度替尼在 60%的患者中需要减量，耐受性差。最常见的 3 级毒性是疲劳（30%）。由于毒性过高，坦度替尼在舒尼替尼或索拉非尼耐药的转移性肾细胞癌患者中不应进一步开发。
