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Clinical Trial
. 2008 Sep 17:8:7.
doi: 10.1186/1472-6904-8-7.

Long-term platinum retention after treatment with cisplatin and oxaliplatin

Elke E M Brouwers  1 , Alwin D R Huitema, Jos H Beijnen, Jan H M Schellens
Affiliations
Clinical Trial

Long-term platinum retention after treatment with cisplatin and oxaliplatin

Elke E M Brouwers et al. BMC Clin Pharmacol. .

Abstract

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).

Conclusion: 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.

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Figures

Figure 1
Figure 1
Pt concentrations of 20 healthy controls (plasma ◆), 20 cancer control patients (plasma ■), 20 cancer patients who were treated with cisplatin 18–73 months before entering this study (plasma ▲ and pUF △), 25 cancer patients who were treated with oxaliplatin 8–23 months before entering this study (plasma ● and pUF ○).
Figure 2
Figure 2
Plasma Pt concentrations versus time since end of treatment.
Figure 3
Figure 3
GFR values for cisplatin treated patients at time of treatment (t = 0) and at follow-up.
Figure 4
Figure 4
GFR values for oxaliplatin treated patients at time of treatment (t = 0) and at follow-up.
See this image and copyright information in PMC

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