Ifosfamide neurotoxicity is related to previous cisplatin treatment for pediatric solid tumors

Neurotoxicity developed in 22 of 97 children and adolescents with malignant solid tumors treated within a phase II ifosfamide protocol. The occurrence of neurotoxicity was related to previous cumulative dosages of cisplatin. One third of the patients who had received more than 600 mg/m2 of cisplatin developed this complication. The relative risk increased 3.2-fold with previous cisplatin dosages above 301 to 600 mg/m2, and 4.1-fold with dosages of 601 to 1,340 mg/m2. The increased risk of neurotoxicity in patients who had received more than 600 mg/m2 of cisplatin may be related to either a decreased clearance of ifosfamide itself or of the drug's active metabolites.