A pharmacogenetic study of aldehyde oxidase I in patients treated with XK469

Pharmacogenet Genomics. 2014 Feb;24(2):129-32. doi: 10.1097/FPC.0000000000000023.


XK469 (NSC 697887) is a selective topoisomerase II β inhibitor eliminated mainly by aldehyde oxidase I (AOX1). We performed a candidate gene study to investigate whether AOX1 genetic variation contributes to interindividual variability in XK469 clearance. Forty-one AOX1 single nucleotide polymorphisms (SNPs) and seven liver expression quantitative trait loci were genotyped in White patients with advanced refractory solid tumors (n=59) and leukemia (n=33). We found a significant decrease in clearance (τ=-0.32, P=0.003) in solid tumor patients with rs10931910, although it failed to replicate in the leukemia cohort (τ=0.18, P=0.20). Four other AOX1 SNPs were associated with clearance (P=0.01-0.02) in only one of the two cohorts. Our study provides a starting point for future investigations on the functionality of AOX1 SNPs. However, variability in XK469 clearance cannot be attributed to polymorphisms in AOX1.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aldehyde Oxidase / genetics*
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacokinetics*
  • Clinical Trials, Phase I as Topic
  • Cohort Studies
  • Genetic Variation
  • Genotype
  • Humans
  • Liver / metabolism*
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Pharmacogenetics
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci
  • Quinoxalines / administration & dosage
  • Quinoxalines / pharmacokinetics*


  • Antineoplastic Agents
  • Quinoxalines
  • XK 469
  • AOX1 protein, human
  • Aldehyde Oxidase