Tumor angiogenesis genotyping and efficacy of first-line chemotherapy in metastatic gastric cancer patients

Pharmacogenomics. 2013 Dec;14(16):1991-8. doi: 10.2217/pgs.13.185. Epub 2013 Oct 3.

Abstract

Aim: Besides correlating with prognosis, tumor-driven angiogenesis also seemed able to influence response/resistance to chemotherapy in preclinical models. We examined the role of tumor angiogenesis genotyping in determining clinical outcome in metastatic gastric cancer patients receiving first-line chemotherapy.

Patients & methods: VEGF-A, VEGF-C, FLT1, KDR and FLT4 genotyping was analyzed in gastric tumors from patients receiving platinum-based first-line chemotherapy.

Results: VEGF-A rs25648 correlated with response rate (partial response: 18% among patients showing the VEGF-A rs25648 CT or TT genotype vs 44% among patients showing the VEGF-A rs25648 C genotype; p = 0.04). At multivariate analysis only VEGF-A rs25648 maintained an independent role in determining median progression-free survival (hazard ratio: 1.65 95% CI: 1.12-2.78) and overall survival (hazard ratio: 1.58, 95% CI: 1.17-2.65).

Conclusion: VEGF-A rs25648 genotyping may help identify a patient subgroup unlikely to benefit from a first-line, platinum-based combination and potential candidates for alternative therapy choices.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Disease-Free Survival
  • Drug Resistance, Neoplasm / genetics
  • Drug Therapy*
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis / drug therapy
  • Neoplasm Metastasis / genetics
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / genetics*
  • Neovascularization, Pathologic / pathology
  • Prognosis
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor C / genetics
  • Vascular Endothelial Growth Factor Receptor-1 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / genetics
  • Vascular Endothelial Growth Factor Receptor-3 / genetics

Substances

  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor C
  • FLT1 protein, human
  • FLT4 protein, human
  • Vascular Endothelial Growth Factor Receptor-1
  • Vascular Endothelial Growth Factor Receptor-2
  • Vascular Endothelial Growth Factor Receptor-3