title: Oxaliplatin-DNA adduct formation in white blood cells of cancer patients.
abstract: 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.
authors.affiliation: Institute of Pharmacy, Department of Clinical Pharmacy, University of Bonn, Bonn, Germany.
authors.forename: A C
authors.initials: AC
authors.lastname: Pieck
authors.forename: A
authors.initials: A
authors.lastname: Drescher
authors.forename: K G
authors.initials: KG
authors.lastname: Wiesmann
authors.forename: J
authors.initials: J
authors.lastname: Messerschmidt
authors.forename: G
authors.initials: G
authors.lastname: Weber
authors.forename: D
authors.initials: D
authors.lastname: Strumberg
authors.forename: R A
authors.initials: RA
authors.lastname: Hilger
authors.forename: M E
authors.initials: ME
authors.lastname: Scheulen
authors.forename: U
authors.initials: U
authors.lastname: Jaehde
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000097:blood* / Q000494:pharmacology; D018736:DNA Adducts / Q000097:blood*; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D009369:Neoplasms / Q000097:blood*; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000097:blood* / Q000494:pharmacology; D000077150:Oxaliplatin
chemical_list: D000970:Antineoplastic Agents; D018736:DNA Adducts; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin