Oxaliplatin-DNA adduct formation in white blood cells of cancer patients

Br J Cancer. 2008 Jun 17;98(12):1959-65. doi: 10.1038/sj.bjc.6604387. Epub 2008 May 27.


In this study, we investigated the kinetics of oxaliplatin-DNA adduct formation in white blood cells of cancer patients in relation to efficacy as well as oxaliplatin-associated neurotoxicity. Thirty-seven patients with various solid tumours received 130 mg m(-2) oxaliplatin as a 2-h infusion. Oxaliplatin-DNA adduct levels were measured in the first cycle using adsorptive stripping voltammetry. Platinum concentrations were measured in ultrafiltrate and plasma using a validated flameless atomic absorption spectrometry method. DNA adduct levels showed a characteristic time course, but were not correlated to platinum pharmacokinetics and varied considerably among individuals. In patients showing tumour response, adduct levels after 24 and 48 h were significantly higher than in nonresponders. Oxaliplatin-induced neurotoxicity was more pronounced but was not significantly different in patients with high adduct levels. The potential of oxaliplatin-DNA adduct measurements as pharmacodynamic end point should be further investigated in future trials.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / blood*
  • Antineoplastic Agents / pharmacology
  • DNA Adducts / blood*
  • Humans
  • Leukocytes / metabolism*
  • Neoplasms / blood*
  • Organoplatinum Compounds / adverse effects
  • Organoplatinum Compounds / blood*
  • Organoplatinum Compounds / pharmacology
  • Oxaliplatin


  • Antineoplastic Agents
  • DNA Adducts
  • Organoplatinum Compounds
  • Oxaliplatin