Long-term platinum retention after treatment with cisplatin and oxaliplatin.
BACKGROUND
The aim of this study was to evaluate long-term platinum retention in patients treated with cisplatin and oxaliplatin.


METHODS
45 patients, treated 8-75 months before participating in this study, were included. Platinum levels in plasma and plasma ultrafiltrate (pUF) were determined. In addition, the reactivity of platinum species in pUF was evaluated. Relationships between platinum retention and possible determinants were evaluated.


RESULTS
Platinum plasma concentrations ranged between 142-2.99 x 10(3) ng/L. Up to 24% of plasma platinum was recovered in pUF. No platinum-DNA adducts in peripheral blood mononuclear cells (PBMCs) could be detected. Ex vivo incubation of DNA with pUF of patients revealed that up to 10% of the reactivity of platinum species was retained. Protein binding proceeded during sample storage. Sodium thiosulfate (STS) appeared to release platinum from the plasma proteins. Platinum levels were related to time, dose, STS co-administration, and glomerular filtration rates (GFR).


CONCLUSIONS
Our data suggest that plasma platinum levels are related to time, age, dose, GFR, and STS use. Platinum in plasma, probably, represent platinum eliminated from regenerating tissue. Platinum species in pUF were partly present in a reactive form. The effects of the reactivity on long-term consequences of Pt-containing chemotherapy, however, remains to be established.
Brouwers
Elke E M
EE
Department of Pharmacy & Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam, The Netherlands. Elke.Brouwers@slz.nl
Huitema
Alwin D R
AD
Beijnen
Jos H
JH
Schellens
Jan H M
JH
D000375:Aging / Q000097:blood; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002945:Cisplatin / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D018736:DNA Adducts / Q000378:metabolism; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D000077150:Oxaliplatin; D010984:Platinum / Q000097:blood* / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D018736:DNA Adducts; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D010984:Platinum; D002945:Cisplatin
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