title: Evaluation of Safety and Efficacy of Salvage Therapy With Sunitinib, Docetaxel (Tyxan) and Cisplatinum Followed by Maintenance Vinorelbine for Unresectable/Metastatic Nonsmall Cell Lung Cancer: Stage 1 of a Simon 2 Stage Clinical Trial. [Corrected].
abstract: 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.
authors.affiliation: 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).
authors.forename: Cheng-Jeng
authors.initials: CJ
authors.lastname: Tai
authors.forename: Chien-Kai
authors.initials: CK
authors.lastname: Wang
authors.forename: Chen-Jei
authors.initials: CJ
authors.lastname: Tai
authors.forename: Ching
authors.initials: C
authors.lastname: Tzao
authors.forename: Yung-Chang
authors.initials: YC
authors.lastname: Lien
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Hsieh
authors.forename: Cheng-I
authors.initials: CI
authors.lastname: Hsieh
authors.forename: Hong-Cheng
authors.initials: HC
authors.lastname: Wu
authors.forename: Chih-Hsiung
authors.initials: CH
authors.lastname: Wu
authors.forename: Chun-Chao
authors.initials: CC
authors.lastname: Chang
authors.forename: Ray-Jade
authors.initials: RJ
authors.lastname: Chen
authors.forename: Hung-Yi
authors.initials: HY
authors.lastname: Chiou
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D000077143:Docetaxel; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects; D016879:Salvage Therapy / Q000379:methods; D000077210:Sunitinib; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077235:Vinorelbine
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D043823:Taxoids; D000077143:Docetaxel; D014747:Vinblastine; D002945:Cisplatin; D000077235:Vinorelbine; D000077210:Sunitinib