Intraperitoneal cis-diamminedichloroplatinum with systemic thiosulfate protection

Area of Science:

• Pharmacology
• Oncology
• Nephrology

Background:

• Cisplatin (cis-diamminedichloroplatinum) is a chemotherapy agent with known toxicities.
• Intraperitoneal (IP) chemotherapy offers a potential route for localized drug delivery.
• Understanding the pharmacokinetics and toxicity of IP cisplatin is crucial for optimizing treatment.

Purpose of the Study:

• To evaluate the toxicity and pharmacokinetics of cisplatin administered via intraperitoneal dialysis.
• To assess the impact of concurrent intravenous sodium thiosulfate on cisplatin toxicity and efficacy.
• To determine the pharmacokinetic advantage of IP cisplatin chemotherapy.

Main Methods:

• Twenty courses of treatment involving cisplatin (90 mg/sq m) via 4-hr IP dialysis.
• Concurrent intravenous infusion of sodium thiosulfate (0.43 or 2.13 g/sq m/hr for 12 hr) in some courses.
• Analysis of cisplatin toxicity and pharmacokinetic parameters (area under the curve ratio).

Main Results:

• Without sodium thiosulfate, cisplatin toxicity was systemic; the peritoneal cavity/plasma area under the curve ratio was 12.
• Intravenous sodium thiosulfate significantly reduced cisplatin-induced nephrotoxicity.
• High cisplatin concentrations in the peritoneal cavity prevented thiosulfate interference with antitumor activity.

Conclusions:

• Intraperitoneal cisplatin chemotherapy exhibits a pharmacokinetic advantage over systemic administration.
• Concurrent sodium thiosulfate effectively mitigates cisplatin's nephrotoxicity.
• IP cisplatin chemotherapy with thiosulfate protection is a promising strategy for localized cancer treatment.