Long-term platinum retention after treatment with cisplatin and oxaliplatin

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.Platinum plasma concentrations ranged between 142–2.99 × 103 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).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.Since its discovery as an effective anticancer agent in the 1960s [1], cisplatin is used extensively in oncology. The use of platinum (Pt) agents has had an enormous impact on the prognosis of several cancer types. After the introduction of cisplatin, mortality of e.g. testicular cancer reduced significantly. Also oxaliplatin has found a widespread use in the treatment of cisplatin resistant colorectal cancer [2].The improved life expectancy of cancer patients treated with Pt-based compounds, has led to an increased interest in the long-term side effects of these drugs, such as peripheral neuropathy, nephrotoxicity, and ototoxicity [3-6]. The presence of long-term side effects has led to the investigation of long-term pharmacokinetics, distribution,