title: Induction chemotherapy with cetuximab, vinorelbine-cisplatin followed by thoracic radiotherapy and concurrent cetuximab, vinorelbine-cisplatin in patients with unresectable stage III non-small cell lung cancer.
abstract: OBJECTIVE
  The modest benefits from concurrent chemoradiotherapy (CCRT) in patients with stage III non-small cell lung cancer (NSCLC) warrant a more effective treatment regimen. We herein report mature data of a phase I/II study testing the addition of cetuximab to induction vinorelbine/cisplatin (NP) followed by concurrent cetuximab NP and thoracic radiation in patients with unresectable stage III NSCLC.
  
  
  METHODS
  Eligible patients were treated with weekly cetuximab (initial dose 400 mg/m2, day 1, week 1; maintenance dose 250 mg/m2 from week 2 to the end of CCRT) and induction vinorelbine (25 mg/m2, days 1 and 8) and cisplatin (75 mg/m2, day 1) every 3 weeks for 2 cycles from week 2. Concomitant thoracic radiation (60-66 Gy/2 Gy) and two cycles of NP (vinorelbine 12.5 mg/m2, days 1 and 8; cisplatin 25mg/m2, days 1 to 3, every 3 weeks) were started from week 7. The primary endpoints were toxicities; the secondary endpoints encompassed response rate and survival.
  
  
  RESULTS
  In total, 27 patients were enrolled, and 24 completed the full regimen. No treatment-related death occurred. Severe (CTCAE Grade 3 or high) adverse events were experienced by 81% patients (22/27), mostly haematologic. Severe non-haematologic toxicities including nausea/vomiting, intestinal obstruction, pulmonary infection and esophagitis, each of which was detected in <7% of patients. With a median follow-up of 26.7 months, the median survival was 26.7 months, with 1- and 2-year survival rates of 88.9% and 51.9%, respectively. Six patients remained progression-free to date, and the median progression-free survival was 13.5 months. The overall response rate was 63% and 77.8% after the induction and CCRT phases, respectively.
  
  
  CONCLUSIONS
  Weekly cetuximab with induction vinorelbine/cisplatin followed by concurrent cetuximab vinorelbine/cisplatin thoracic radiation is feasible with a manageable toxicity profile and clinically active.
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Di
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Zhejiang Cancer Hospital, Zhejiang, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital to Nanjing Medical University, Jiangsu, China.
authors.forename: Jiayan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, Zhejiang Cancer Hospital, Zhejiang, China.
authors.forename: Guan
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Zhejiang Cancer Hospital, Zhejiang, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Liyi
authors.initials: L
authors.lastname: Xie
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Weixin
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Jiang
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China. Electronic address: fanming@fudan.edu.cn.
authors.forename: Min
authors.initials: M
authors.lastname: Fan
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D000068818:Cetuximab / Q000008:administration & dosage; D059248:Chemoradiotherapy / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D014747:Vinblastine; D000068818:Cetuximab; D002945:Cisplatin; D000077235:Vinorelbine
keywords: Cetuximab; Concurrent chemoradiotherapy; Induction chemotherapy; Locally advanced; Non-small cell lung cancer