A Phase I Trial of Sunitinib and Rapamycin in Patients with Advanced Non-Small Cell Lung Cancer

作者：Waqar Saiama N; Gopalan Priya K; Williams Kristina; Devarakonda Siddhartha; Govindan Rarnaswamy^*

来源：Chemotherapy, 2013, 59(1): 8-13.

DOI：10.1159/000348584

• Sunitinib
• Rapamycin
• Non-small cell lung cancer
• Phase I trial

Background: 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. Methods: We performed a phase I study evaluating the combination of sunitinib and rapamycin in patients with advanced NSCLC. Results: 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. Conclusion: The combination of sunitinib and rapamycin is well-tolerated and warrants further investigation in the phase II setting.

• 出版日期2013