Effects of single nucleotide polymorphisms on treatment outcomes and toxicity in patients treated with sunitinib

Anticancer Res. 2013 Oct;33(10):4619-26.

Abstract

Background/aim: We analyzed the efficacy and toxicity profile of sunitinib according to single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor receptor (VEGFR) and Kinase insert domain receptor (KDR).

Patients and methods: We examined eight known SNPs of VEGFA and five SNPs of KDR among patients with gastric or biliary tract cancer who were treated with sunitinib. We retrospectively assessed clinical outcomes and their relationships to these SNPs.

Results: A total of 63 patients were evaluable. Among candidate SNPs, rs2010963 and rs833068 of VEGFA, and rs1870377 of KDR were associated with poor time to treatment failure (TTF) (p=0.009, 0.002, and 0.029, respectively), while rs1870377 and rs7692791 of KDR were associated with poor overal survival (OS) (p=0.001 and 0.03, respectively). Multivariate analysis showed that only rs1870377 had significant effects on both TTF and OS. Toxicity evaluation indicated that rs1531289 of KDR was associated with grade 3-4 anemia. (p=0.021).

Conclusion: Certain SNPs of KDR may affect treatment outcome and toxicity in patients treated with sunitinib.

Keywords: Single nucleotide polymorphism; VEGF; VEGFR; biliary tract cancer; gastric cancer; sunitinib.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Biliary Tract Neoplasms / drug therapy*
  • Biliary Tract Neoplasms / genetics
  • Biliary Tract Neoplasms / mortality
  • Disease-Free Survival
  • Female
  • Genetic Association Studies
  • Homozygote
  • Humans
  • Indoles / adverse effects
  • Indoles / therapeutic use*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Proportional Hazards Models
  • Pyrroles / adverse effects
  • Pyrroles / therapeutic use*
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / mortality
  • Sunitinib
  • Treatment Failure
  • Vascular Endothelial Growth Factor A / genetics*
  • Vascular Endothelial Growth Factor Receptor-2 / genetics*

Substances

  • Antineoplastic Agents
  • Indoles
  • Pyrroles
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-2
  • Sunitinib