Oxaliplatin-DNA adduct formation in white blood cells of cancer patients.
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.
Pieck
A C
AC
Institute of Pharmacy, Department of Clinical Pharmacy, University of Bonn, Bonn, Germany.
Drescher
A
A
Wiesmann
K G
KG
Messerschmidt
J
J
Weber
G
G
Strumberg
D
D
Hilger
R A
RA
Scheulen
M E
ME
Jaehde
U
U
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
D000970:Antineoplastic Agents; D018736:DNA Adducts; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin