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High-dose cisplatin with sodium thiosulfate protection.
Summary
Sodium thiosulfate protects against cisplatin nephrotoxicity, allowing for higher doses. This study found that concurrent thiosulfate administration enabled a twofold increase in cisplatin dose and exposure without altering pharmacokinetics.
Area of Science:
- Oncology
- Pharmacology
- Nephrology
Background:
- Nephrotoxicity is a major dose-limiting factor for cisplatin chemotherapy.
- Sodium thiosulfate is a known neutralizer of cisplatin and offers renal protection.
Purpose of the Study:
- To investigate if sodium thiosulfate administration allows for escalated cisplatin dosing.
- To assess the impact of concurrent thiosulfate on cisplatin pharmacokinetics.
Main Methods:
- A fixed dose of sodium thiosulfate (9.9 g/m2) was administered intravenously over 3 hours.
- Escalating doses of cisplatin were given during the final 2 hours of the thiosulfate infusion.
- Cisplatin pharmacokinetics were compared between patients receiving high-dose cisplatin with thiosulfate and standard-dose cisplatin without thiosulfate.
Main Results:
- Cisplatin doses were escalated up to 225 mg/m2 with thiosulfate before dose-limiting toxicities occurred.
- Concurrent thiosulfate administration resulted in a twofold increase in total drug exposure.
- No significant changes in cisplatin elimination rate constant, volume of distribution, or total body clearance were observed.
Conclusions:
- Concurrent administration of sodium thiosulfate permits a significant increase in cisplatin dose and exposure.
- This strategy may enhance the efficacy of cisplatin chemotherapy by allowing higher, potentially more effective, doses.