*Department of Urology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka-shi, Iwate 020-8505, Japan.
Jpn J Clin Oncol. 2014 May;44(5):479-85. doi: 10.1093/jjco/hyu018. Epub 2014 Mar 30.
Everolimus is positioned as second-line treatment for metastatic renal cell carcinoma resistant to vascular endothelial growth factor receptor-tyrosine kinase inhibitors. We investigated retrospectively the efficacy and safety of everolimus in Japanese patients with advanced renal cell carcinoma in the clinical setting.
Nineteen patients who discontinued treatment with vascular endothelial growth factor receptor-tyrosine kinase inhibitors because of disease progression or adverse events were administered everolimus. We evaluated progression-free survival, overall survival and tumor response rate of everolimus treatment. We also compared laboratory abnormalities and adverse events of everolimus treatment with those of prior vascular endothelial growth factor receptor-tyrosine kinase inhibitors therapy.
In all patients, median progression-free survival was 8.4 months and median overall survival was not reached at 25 months. The best objective response was complete response in 1 patient and stable disease in 15 patients. Eleven patients (58%) were intolerant and 8 (42%) were refractory to prior vascular endothelial growth factor receptor-tyrosine kinase inhibitors treatment. Median overall survival was significantly longer (P < 0.01) in vascular endothelial growth factor receptor-tyrosine kinase inhibitor-intolerant (>25 months) than in vascular endothelial growth factor receptor-tyrosine kinase inhibitor-refractory subjects (4.3 months), and median progression-free survival tended to be better (P= 0.06) in vascular endothelial growth factor receptor-tyrosine kinase inhibitor-intolerant (10.0 months) than in vascular endothelial growth factor receptor-tyrosine kinase inhibitor-refractory subjects (2.5 months). Two patients discontinued everolimus treatment because of adverse events.
In this study, the overall survival and progression-free survival were better in vascular endothelial growth factor receptor-tyrosine kinase inhibitor-intolerant than in vascular endothelial growth factor receptor-tyrosine kinase inhibitor-refractory subjects. The adverse event profiles of everolimus and vascular endothelial growth factor receptor-tyrosine kinase inhibitors were different. Patients intolerant to vascular endothelial growth factor receptor-tyrosine kinase inhibitors may tolerate everolimus well and have greater survival benefit from switching to everolimus than those refractory to vascular endothelial growth factor receptor-tyrosine kinase inhibitors.
依维莫司被定位为血管内皮生长因子受体酪氨酸激酶抑制剂耐药的转移性肾细胞癌的二线治疗药物。我们回顾性研究了依维莫司在日本晚期肾细胞癌患者中的疗效和安全性。
19 名因疾病进展或不良反应而停止血管内皮生长因子受体酪氨酸激酶抑制剂治疗的患者接受了依维莫司治疗。我们评估了依维莫司治疗的无进展生存期、总生存期和肿瘤缓解率。我们还比较了依维莫司治疗的实验室异常和不良反应与血管内皮生长因子受体酪氨酸激酶抑制剂治疗的实验室异常和不良反应。
所有患者的中位无进展生存期为 8.4 个月，25 个月时中位总生存期未达到。最佳客观缓解为 1 例完全缓解，15 例稳定疾病。11 例（58%）患者不耐受，8 例（42%）患者对血管内皮生长因子受体酪氨酸激酶抑制剂治疗有耐药性。血管内皮生长因子受体酪氨酸激酶抑制剂不耐受（>25 个月）患者的中位总生存期明显长于血管内皮生长因子受体酪氨酸激酶抑制剂耐药患者（4.3 个月）（P<0.01），血管内皮生长因子受体酪氨酸激酶抑制剂不耐受患者的中位无进展生存期也有改善趋势（P=0.06）（10.0 个月）比血管内皮生长因子受体酪氨酸激酶抑制剂耐药患者（2.5 个月）。两名患者因不良反应停止了依维莫司治疗。
在这项研究中，血管内皮生长因子受体酪氨酸激酶抑制剂不耐受患者的总生存期和无进展生存期优于血管内皮生长因子受体酪氨酸激酶抑制剂耐药患者。依维莫司和血管内皮生长因子受体酪氨酸激酶抑制剂的不良反应谱不同。对血管内皮生长因子受体酪氨酸激酶抑制剂不耐受的患者可能对依维莫司耐受良好，与血管内皮生长因子受体酪氨酸激酶抑制剂耐药患者相比，从血管内皮生长因子受体酪氨酸激酶抑制剂转换为依维莫司具有更大的生存获益。
