Pharmacogenetics of telatinib, a VEGFR-2 and VEGFR-3 tyrosine kinase inhibitor, used in patients with solid tumors

Invest New Drugs. 2011 Feb;29(1):137-43. doi: 10.1007/s10637-009-9347-0. Epub 2009 Nov 19.


Purpose: Telatinib is an orally active small-molecule tyrosine kinase inhibitor of kinase insert domain receptor (KDR; VEGFR-2) and fms-related tyrosine kinase 4 (FLT4; VEGFR-3). This study aims at the identification of relationships between single nucleotide polymorphisms (SNPs) in genes encoding for transporter proteins and pharmacokinetic parameters in order to clarify the significant interpatient variability in drug exposure. In addition, the potential relationship between target receptor polymorphisms and toxicity of telatinib is explored.

Methods: Blood samples from 33 patients enrolled in a phase I dose-escalation study of telatinib were analyzed. For correlation with dose normalized AUC(0-12), ATP-binding cassette (ABC) B1 (ABCB1), ABCC1, and ABCG2 were the genes selected. For correlation with telatinib toxicity, selected genes were the drug target genes KDR and FLT4.

Results: No association between dose normalized AUC(0-12) and drug transporter protein polymorphisms was observed. In addition, no association between toxicity and KDR or FLT4 genotype or haplotype was seen.

Conclusions: Our pharmacogenetic analysis could not reveal a correlation between relevant gene polymorphisms and clinical and pharmacokinetic observations of telatinib.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Area Under Curve
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology*
  • Neoplasms / genetics
  • Pharmacogenetics
  • Polymorphism, Single Nucleotide / genetics*
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyridazines / administration & dosage
  • Pyridazines / adverse effects
  • Pyridazines / pharmacokinetics
  • Pyridazines / therapeutic use*
  • Pyridines / administration & dosage
  • Pyridines / adverse effects
  • Pyridines / pharmacokinetics
  • Pyridines / therapeutic use*
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor Receptor-2 / genetics
  • Vascular Endothelial Growth Factor Receptor-3 / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor Receptor-3 / genetics
  • Young Adult


  • Protein Kinase Inhibitors
  • Pyridazines
  • Pyridines
  • telatinib
  • Vascular Endothelial Growth Factor Receptor-2
  • Vascular Endothelial Growth Factor Receptor-3