Central Nervous System Toxicity Following the Treatment of Pediatric Patients with Ifosfamide/mesna

Ifosfamide/mesna treatment of 50 patients with pediatric malignant solid tumors was associated with the development of neurotoxic signs and symptoms in 11 of these individuals who received 29 courses of treatment. Neurologic toxicity included changes in mental status, cerebellar function, cranial nerve, and cerebellar and motor system function, including seizures. All symptoms, signs, and EEG abnormalities were transient. Some of the affected individuals failed to develop acute neurotoxic signs of symptoms when retreated with ifosfamide. A grading system for scoring these neurologic abnormalities is presented for comparison of acute neurotoxic effects of other agents. Recommendations are made regarding early termination or delay of ifosfamide/mesna treatments in the presence of significant neurotoxicity.