CYTOTOXIC EFFECTS OF LONG-TERM CIRCULATING ULTRAFILTERABLE PLATINUM SPECIES AND LIMITED EFFICACY OF HEMODIALYSIS IN CLEARING THEM

We applied haemodialysis to clear platinum (Pt) circulating species fo llowing renal insufficiency due to an accidental cisplatin overdosage (205 mg/m(2) instead of 100 mg/m(2)). Serum samples were repeatedly ob tained during this clinical episode from day 5 up to day 30 after cisp latin dosing. A serum aliquot taken at day 22 after cisplatin administ ration was tested to assess the possible cytotoxicity exhibited by the circulating Pt species on a head and neck tumour cell line. The profi le of ultrafiltrable (UF) Pt during successive haemodialysis cycles wa s striking. After each haemodialysis cycle, a marked decrease in UF Pt , occurred but was followed by more or less pronounced rebounds. Cispl atin concentration-cytotoxic effect curves obtained in vitro from pati ent serum before cisplatin administration and healthy control serum ex hibited very similar concentration effect profiles. In contrast, the p atient serum taken at day 22 after cisplatin administration resulted i n marked cytotoxic effects, which were much greater than those which c ould have been anticipated considering the Pt concentration of this se rum sample. The present report underlines the limited usefulness of ha emodialysis for rescuing cisplatin treated patients, exhibiting unanti cipated postinfusion renal failure with overexposure to the drug. The in vitro investigations suggest that pharmacological effects of Pt der ivatives may not only be attributable to short-term effects of the dru g diffusion into tissues, but also to more delayed effects from Pt cir culating species.