Plasma platinum levels: relationship to cisplatin dose and nephrotoxicity

Renal dysfunction is the dose-limiting toxic effect for many patients receiving cisplatin (CP). Despite hydration and/or forced diuresis, some patients develop nephrotoxicity, and patients at risk cannot be easily identified. We studied 77 patients with several types of carcinoma who received 115 cycles of CP, by 24-hour infusion, at doses of 40-100 mg/m2. Blood samples for platinum (Pt) analysis were obtained during and after CP infusion; plasma Pt levels were dose- and time-dependent. A significant rise in serum creatinine was seen after the first cycle and cumulatively over subsequent CP cycles. The largest subgroup of patients, those who received 80 mg/m2, was analyzed for predictors of nephrotoxicity. Twenty-five percent of patients exhibited nephrotoxicity (greater than 30% rise in serum creatinine or greater than 30% fall in creatinine clearance). These nephrotoxic patients had significantly higher plasma Pt levels during CP infusion than did nonnephrotoxic patients. Age, sex, cycle number, and pretreatment creatinine did not predict nephrotoxicity. Patients predisposed to nephrotoxicity with CP chemotherapy may be identifiable, on the basis of elevated plasma Pt, early in the course of CP infusion.