Controlling angiogenesis in gastric cancer: A systematic review of anti-angiogenic trials

Cancer Lett. 2016 Oct 1;380(2):598-607. doi: 10.1016/j.canlet.2015.12.023. Epub 2015 Dec 24.

Abstract

Purpose: Angiogenesis is a promising therapeutic target to inhibit tumor growth. This review summarizes data from clinical trials of anti-angiogenic agents in gastric cancer.

Design: A systematic search of PubMed, Embase and conference databases is performed to identify clinical trials with specific anti-angiogenic agents in gastric cancer treatment

Results: The risk of disease progression (37-52%) and death (19-22%) with ramucirumab as second-line treatment decreases in phase III trials in advanced gastric cancer. No significant improvement in overall survival (OS) with the addition of bevacizumab to chemotherapy is shown. Bevacizumab or ramucirumab combined with traditional chemotherapy is associated with higher adverse event rate compared to chemotherapy alone. Except for apatinib, phase II trials of other tyrosine kinase inhibitors (TKIs) may improve overall response rate, but there are no significant improvements in OS and progression-free survival (PFS) when combined with chemotherapy.

Conclusion: Phase III trials in advanced gastric cancer have demonstrated improved outcome with ramucirumab as second-line treatment. Most of the other studies on anti-angiogenic agents in gastric cancer have reported improvement in response rate but not in OS compared to chemotherapy alone. Future research is expected in optimizing the anti-angiogenic therapy combined with traditional treatment.

Keywords: Angiogenesis inhibitors; Antineoplastic agents; Antineoplastic combined chemotherapy protocols; Controlled clinical trial; Gastric neoplasms; Vascular endothelial growth factor antagonists and inhibitors.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / therapeutic use*
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Clinical Trials as Topic*
  • Humans
  • Molecular Targeted Therapy
  • Neovascularization, Pathologic*
  • Protein Kinase Inhibitors / therapeutic use
  • Signal Transduction / drug effects
  • Stomach Neoplasms / blood supply*
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Treatment Outcome
  • Tumor Microenvironment

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Protein Kinase Inhibitors