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

Clin Transl Oncol. 2015 May;17(5):371-7. doi: 10.1007/s12094-014-1241-3. Epub 2014 Oct 29.

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.

Patients and materials: 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.

Conclusion: The use of PKC inhibitors in addition to chemotherapy was not a valid alternative for patients with advanced NSCLC.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Disease-Free Survival
  • Humans
  • Indoles / administration & dosage
  • Indoles / adverse effects
  • Lung Neoplasms / drug therapy*
  • Phosphorothioate Oligonucleotides / administration & dosage
  • Phosphorothioate Oligonucleotides / adverse effects
  • Protein Kinase C / antagonists & inhibitors*
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / adverse effects
  • Randomized Controlled Trials as Topic
  • Survival Rate

Substances

  • Indoles
  • Phosphorothioate Oligonucleotides
  • Protein Kinase Inhibitors
  • Protein Kinase C
  • aprinocarsen
  • enzastaurin