Intraperitoneal c/s-Diamminedichloroplatinum with Systemic Thiosulfate Protection1

The toxicity and pharmacokinetics of c/s-diamminedichloroplatinum (cisplatin) (90 mg/sq m) administered as a single 4hr peritoneal dialysis, with or without concurrent i.v. infusion of sodium thiosulfate, 0.43 or 2.13 g/sq m/hr for 12 hr, were studied on 20 courses of treatment. When given without thio sulfate, the toxicity of cisplatin was systemic rather than local, and the peritoneal cavity/plasma ratio of the area under the curve was 12. Addition of i.v. thiosulfate significantly reduced the nephrotoxicity. The concentration of cisplatin in the peri toneal cavity was sufficiently greater than that in the plasma to prevent thiosulfate, which equilibrated into the cavity, from interfering with the antitumor activity of cisplatin in the perito neum. This study demonstrates a pharmacokinetic advantage of i.p. chemotherapy with cisplatin.