Nephrotoxicity of high-dose intracavitary cisplatin with intravenous thiosulfate protection

Abstract Sodium thiosulfate has been shown experimenally to protect against cisplatin-induced renal insufficiency by inactivating the nephrotoxic as well as cytotoxic properties of the agent. However, significant plasma levels of ‘active’ cisplatin have been demonstrated following high-dose intracavitary cisplatin administration with simultaneous intravenous thiosulfate delivery. At the UCSD Cancer Center 131 patients have been treated with a total of 485 courses (median per patient, 3; range 1–18) of intrapleural or intraperitoneal cisplatin with intravenous thiosulfate protection. Seventy-six patiens (58%) had previously been treated with intravenous cisplatin. A total of 14 courses (2.9%) of intracavitary therapy were complicated by a serum creatinine rise to >1.5 mg % which, in all but three cases, returned to the normal range within 1 month following treatment. All but one patient demonstrating clinical evidence of nephrotoxicity had been heavily pretreated with cisplatin. We conclude that thiosulfate can protect against clinically significant cisplatin-induced nephrotoxicity by cisplatin delivered in high doses via the intracavitary route.