Division of Medical Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Chemotherapy. 2013;59(1):8-13. doi: 10.1159/000348584. Epub 2013 Apr 26.
Sunitinib is an oral multitargeted tyrosine kinase inhibitor, with single-agent activity in non-small cell lung cancer (NSCLC). Resistance to tyrosine kinase inhibitor therapy is mediated by the mammalian target of rapamycin (mTOR) pathway, and may be reversed by using mTOR inhibitors.
We performed a phase I study evaluating the combination of sunitinib and rapamycin in patients with advanced NSCLC.
Nineteen patients were enrolled in the study. The dose-limiting toxicities included infection, pneumonia, diarrhea/dehydration and treatment delay due to thrombocytopenia in 1 patient each. Sunitinib 25 mg orally daily and rapamycin 2 mg orally daily with 4 weeks on and 2 weeks off therapy were determined to be the maximum tolerated dose. No objective responses were noted, and 6 patients had stable disease as a best response.
The combination of sunitinib and rapamycin is well-tolerated and warrants further investigation in the phase II setting.
舒尼替尼是一种口服的多靶点酪氨酸激酶抑制剂，在非小细胞肺癌（NSCLC）中具有单药活性。对酪氨酸激酶抑制剂治疗的耐药性是由哺乳动物雷帕霉素靶蛋白（mTOR）途径介导的，并且可以通过使用 mTOR 抑制剂来逆转。
我们进行了一项 I 期研究，评估舒尼替尼和雷帕霉素联合用于晚期 NSCLC 患者。
19 名患者入组该研究。1 例患者因感染、肺炎、腹泻/脱水和血小板减少导致剂量限制性毒性；1 例患者因感染、肺炎、腹泻/脱水和治疗延迟导致剂量限制性毒性。确定舒尼替尼 25mg 每日口服和雷帕霉素 2mg 每日口服，4 周为一个周期，2 周停药为最大耐受剂量。未观察到客观缓解，6 例患者的最佳反应为疾病稳定。
舒尼替尼和雷帕霉素的联合使用耐受性良好，值得在 II 期研究中进一步探索。
