Potentiation of ifosfamide neurotoxicity, hematotoxicity, and tubular nephrotoxicity by prior cis-diamminedichloroplatinum(II) therapy.

We investigated the relationship between prior therapy and three distinct forms of toxicity that developed during ifosfamide administration (1.6 g/m2/day for 5 days) in 36 children with malignant solid tumors. Of ten therapies that were studied by multiple regression techniques, only the number of doses of cisplatin that patients had received was significantly related to neurotoxicity, hematotoxicity, and tubular nephrotoxicity, with the more severe cases occurring after three or more doses (P less than 0.05). Increased urinary concentrations of the renal tubular enzyme N-acetyl-beta-D-glucosaminidase, measured before each course of ifosfamide, were predictive of neurotoxicity (P = 0.02) and hematotoxicity (P = 0.01). We suggest that cisplatin-induced renal tubular damage, leading to the impaired clearance of ifosfamide metabolites, may account for this added toxicity.