title: The protein kinase C (PKC) inhibitors combined with chemotherapy in the treatment of advanced non-small cell lung cancer: meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  The application of newer signaling pathway-targeted agents has become an important addition to chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC). In this study, we evaluated the efficacy and toxicities of PKC inhibitors combined with chemotherapy versus chemotherapy alone for patients with advanced NSCLC systematically.
  
  
  METHODS
  Literature retrieval, trials selection and assessment, data collection, and statistic analysis were performed according to the Cochrane Handbook 5.1.0. The outcome measures were tumor response rate, disease control rate, progression-free survival (PFS), overall survival (OS), and adverse effects.
  
  
  RESULTS
  Five randomized controlled trials, comprising totally 1,005 patients, were included in this study. Meta-analysis showed significantly decreased response rate (RR 0.79; 95 % CI 0.64-0.99) and disease control rate (RR 0.90; 95 % CI 0.82-0.99) in PKC inhibitors-chemotherapy groups versus chemotherapy groups. There was no significant difference between the two treatment groups regarding progression-free survival (PFS, HR 1.05; 95 % CI 0.91-1.22) and overall survival (OS, HR 1.00; 95 % CI 0.86-1.16). The risk of grade 3/4 neutropenia, leucopenia, and thrombosis/embolism increased significantly in PKC inhibitors combination groups as compared with chemotherapy alone groups.
  
  
  CONCLUSIONS
  The use of PKC inhibitors in addition to chemotherapy was not a valid alternative for patients with advanced NSCLC.
authors.affiliation: Department of Oncology, Tianjin Medical University General Hospital, #154 Anshan Road, Heping District, Tianjin, 300052, China, zllcaroline@163.com.
authors.forename: L L
authors.initials: LL
authors.lastname: Zhang
authors.forename: F F
authors.initials: FF
authors.lastname: Cao
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: F L
authors.initials: FL
authors.lastname: Meng
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: D S
authors.initials: DS
authors.lastname: Zhong
authors.forename: Q H
authors.initials: QH
authors.lastname: Zhou
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D018572:Disease-Free Survival; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects; D008175:Lung Neoplasms / Q000188:drug therapy*; D054735:Phosphorothioate Oligonucleotides / Q000008:administration & dosage / Q000009:adverse effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D015996:Survival Rate
chemical_list: D007211:Indoles; D054735:Phosphorothioate Oligonucleotides; D047428:Protein Kinase Inhibitors; D011493:Protein Kinase C; C488084:aprinocarsen; C504878:enzastaurin