title: Chemotherapy plus Vandetanib or chemotherapy alone in advanced non-small cell lung cancer: a meta-analysis of four randomised controlled trials.
abstract: OBJECTIVE
  Most patients with advanced non-small cell lung cancer (NSCLC) require systemic chemotherapy. Vandetanib, targeting epidermal growth factor receptor and vascular endothelial growth factor receptor signalling in NSCLC, has recently been evaluated in combination chemotherapy in advanced NSCLC. However, the advantage of chemotherapy plus vandetanib over chemotherapy alone in advanced NSCLC remains largely unknown. A meta-analysis of randomised controlled trials was carried out to compare the efficacy and toxicity of chemotherapy plus vandetanib with chemotherapy alone in advanced NSCLC.
  
  
  METHODS
  The PubMed database, American Society of Clinical Oncology, European Society for Medical Oncology and the Cochrane Library and references of published trials were searched. Two reviewers independently assessed the quality of the trials. Data were extracted and the overall response rate, pooled progression-free survival, overall survival with 95% confidence intervals and main toxicity were analysed.
  
  
  RESULTS
  Four randomised controlled trials involving 2160 patients with advanced NSCLC were ultimately analysed. Compared with chemotherapy alone, chemotherapy plus vandetanib significantly increased the overall response rate (relative risk = 1.96, 95% confidence interval = 1.53--2.52) and progression-free survival (hazard ratio = 0.79, 95% confidence interval = 0.71-0.87), but there was no significant difference in overall survival (hazard ratio = 0.91, 95% confidence interval = 0.79-1.03). Patients who received chemotherapy plus vandetanib had more rash, diarrhoea, hypertension and QTc prolongation (odds ratio = 2.32, 95% confidence interval = 1.93-2.79; odds ratio = 1.64, 95% confidence interval = 1.37-1.97; odds ratio = 4.08, 95% confidence interval = 2.51-6.01, odds ratio = 17.77, 95% confidence interval = 3.54-61.66, respectively), and less nausea and vomiting (odds ratio = 0.70, 95% confidence interval = 0.58-0.85; odds ratio = 0.69, 95% confidence interval = 0.55-0.86, respectively). The incidences of haemorrhage, fatigue and cough were comparable between the two groups.
  
  
  CONCLUSIONS
  Although similar in overall survival, chemotherapy plus vandetanib showed particular advantages over chemotherapy alone in terms of progression-free survival and overall response rate. The toxicity was comparable between the two groups. Therefore, chemotherapy plus vandetanib might be a safe and valid therapeutic option for advanced NSCLC patients.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Yong-Ying
authors.initials: YY
authors.lastname: Xiao
authors.forename: Ping
authors.initials: P
authors.lastname: Zhan
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Yuan
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Liu
authors.forename: Tang-Feng
authors.initials: TF
authors.lastname: Lv
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
authors.forename: Yong
authors.initials: Y
authors.lastname: Song
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D010880:Piperidines / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D040262:Receptors, Vascular Endothelial Growth Factor; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D010880:Piperidines; D011799:Quinazolines; D040262:Receptors, Vascular Endothelial Growth Factor; C452423:vandetanib