A phase I study in paediatric patients to evaluate the safety and pharmacokinetics of SPI-77, a liposome encapsulated formulation of cisplatin

Pre-clinical studies indicate that cisplatin encapsulated in STEALTH(R) lip osomes (SPI-77) retains anti-tumour activity, but has a much reduced toxici ty, compared to native cisplatin. A phase I study was conducted to determin e the toxicity and pharmacokinetics of SPI-77 administered to children with advanced cancer not amenable to other treatment. Paediatric patients were treated at doses ranging from 40 to 320 mg m(-2) by intravenous infusion ev ery 4 weeks. Blood samples taken during, and up to 3 weeks after, administr ation and plasma and ultrafiltrate were prepared immediately. Urine was col lected, when possible, for 3 days after administration. SPI-77 administrati on was well tolerated with the major toxicity being an infusion reaction wh ich responded to modification of the initial infusion rate of SPI-77. Limit ed haematological toxicity and no nephrotoxicity were observed. No response s to treatment were seen during the course of this phase I study. Measureme nt of total plasma platinum showed that cisplatin was retained in the circu lation with a half life of up to 134 h, with maximum plasma concentrations approximately 100-fold higher than those reported following comparable dose s of cisplatin. Comparison of plasma and whole blood indicated that cisplat in was retained in the liposomes and there was no free platinum measurable in the ultrafiltrate. Urine recovery was less than 4% of the dose administe red over 72 h. Results from this phase I study indicate that high doses of liposomal cisplatin can safely be given to patients, but further studies ar e required to address the issue of reformulation of liposomally bound cispl atin. (C) 2001 Cancer Research Campaign.