Evolution of high-dose cisplatin.

High-dose cisplatin therapy, defined as 200 mg/m2/course, is currently undergoing extensive clinical trials in a variety of solid tumors. The reduction of the incidence and severity of cisplatin-induced nephrotoxicity has led to clinical trials of higher doses of cisplatin. By maintaining nephrotoxicity to acceptable levels, dose response relationships have shown increased efficacy of cisplatin therapy. However, new dose-limiting toxicities, primarily severe neurotoxicity and myelosuppression, have prevented further dosing increases. The following review will trace the evolution and the current status of high-dose cisplatin therapy. In addition, a summary of the dose-limiting non-renal toxicities and their relationship to pharmacokinetics and dosing schedules will be discussed.