Tai Cheng-Jeng, Wang Chien-Kai, Tai Chen-Jei, Tzao Ching, Lien Yung-Chang, Hsieh Chih-Cheng, Hsieh Cheng-I, Wu Hong-Cheng, Wu Chih-Hsiung, Chang Chun-Chao, Chen Ray-Jade, Chiou Hung-Yi
From the Division of Hematology and Oncology, Department of Internal Medicine (C-JT, C-KW, C-IH, H-CW), Department of Chinese Medicine (C-KW, C-JT), Traditional Herbal Medicine Research Center (C-JT), Division of Thoracic Surgery, Department of Surgery (CT, Y-CL), Division of Gastroenterology, Department of Internal Medicine (C-CC), and Division of General Surgery, Department of Surgery (R-JC), Taipei Medical University Hospital, Taipei, Taiwan; Department of Internal Medicine, School of Medicine, College of Medicine (C-JT, C-KW, C-IH, H-CW, C-CC), Department of Obstetrics and Gynecology, School of Medicine, College of Medicine (C-KW, C-JT), Graduate Institute of Clinical Medicine, College of Medicine (CT), Department of Surgery, School of Medicine, College of Medicine (Y-CL, C-HW, R-JC), Center of Excellence for Cancer Research (C-HW), and School of Public Health, College of Public Health and Nutrition (H-YC), Taipei Medical University, Taipei, Taiwan; Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan (C-CH), and Department of Surgery, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan (C-HW).
Medicine (Baltimore). 2015 Dec;94(52):e2303. doi: 10.1097/MD.0000000000002303.
Current chemotherapeutic regimens for nonsmall cell lung cancer (NSCLC) have reached a plateau over the last few years. Targeted therapy makes use of tyrosine kinase inhibitors (TKIs) to suppress a number of signaling pathways including epidermal growth factor receptor and vascular endothelial growth factor which are active in NSCLC biology. In this study, we used sunitinib, a multi-target receptor TKI, combined with chemotherapy for unresectable/metastatic NSCLC.This open label Simon's 2 stage clinical trial enrolled a total of 6 NSCLC patients who received docetaxel (40 mg) and cisplatin (50 mg) on day 1 of each cycle (14 day interval between cycles) and sunitinib (25 mg qd for 10 days between cycles) for a total of 12 cycles (24 weeks), after which patients received maintenance therapy with vinorelbine (30 mg TIW) until disease progression. The sample size was based on a Simon's Optimal Two-Stage Designs for Phase II clinical trials. The expected response rate was set as 35% for P0 and as 60% for P1. The study was designed for a minimum of 6 patients for first stage and 15 patients until second stage with a significance level alpha = 0.10 and power = 70%. Diagnosis of a poor response in the second of 6 patients in Stage I or seventh of the 15 patients in Stage II would lead to early termination of the trial.The overall response rate was 66.7%. Four patients had an overall survival >60 months. The time to PFS ranged from 3 to 42 months. The combination therapy was well-tolerated.Sunitinib combined with chemotherapy shows promise and warrants further investigation.
在过去几年中,非小细胞肺癌(NSCLC)的现行化疗方案已达到瓶颈。靶向治疗利用酪氨酸激酶抑制剂(TKIs)来抑制多种信号通路,包括在NSCLC生物学中活跃的表皮生长因子受体和血管内皮生长因子。在本研究中,我们使用多靶点受体TKI舒尼替尼联合化疗治疗不可切除/转移性NSCLC。这项开放标签的西蒙两阶段临床试验共纳入了6例NSCLC患者,他们在每个周期的第1天接受多西他赛(40mg)和顺铂(50mg)(周期之间间隔14天),并在周期之间的10天内每天服用舒尼替尼(25mg),共12个周期(24周),之后患者接受长春瑞滨(30mg,每周3次)维持治疗直至疾病进展。样本量基于西蒙II期临床试验的最优两阶段设计。预期缓解率设定为P0为35%,P1为60%。该研究设计为第一阶段至少6例患者,第二阶段直至15例患者,显著性水平α = 0.10,检验效能 = 70%。如果在第一阶段的6例患者中的第2例或第二阶段的15例患者中的第7例被诊断为反应不佳,将导致试验提前终止。总缓解率为66.7%。4例患者总生存期>60个月。无进展生存期为3至42个月。联合治疗耐受性良好。舒尼替尼联合化疗显示出前景,值得进一步研究。