A PHASE-I STUDY OF IFOSFAMIDE GIVEN ON ALTERNATE DAYS TO TREAT CHILDREN WITH BRAIN-TUMORS

Background. Ifosfamide with Mesna, given every other day over a 5-day period, was evaluated in 20 children with recurrent or progressive primary brain tumors. Methods, The patients were assigned to dosage cohorts separated on the basis of prior exposure to cisplatin (n = 10) or the absence of such exposure (n = 10). The initial dose in each treatment arm was 2133 mg/m2 every other day for three doses, which represented 80% of the total dose delivered in our prior study of ifosfamide given daily over 5 days. The dose was escalated by 20% in each of the two subsequent cohorts (2560 mg/m2 and 3072 mg/m2 every other day for three doses). Results. The hematologic toxicity was dose limiting. Prior exposure to cisplatin did not seem to increase the hematologic toxicity. The most frequent and significant metabolic disturbance was hyponatremia, resulting in self-limited seizure activity in three patients. This complication was prevented in subsequent patients by changing the postifosfamide hydration fluids from 5% dextrose in quarter normal saline to 5% dextrose in normal saline. Conclusions. Although no child achieved a complete response, the activity of ifosfamide was demonstrated for a variety of tumors. The recommended dose of ifosfamide in a Phase II study for brain tumors is 3000 mg/m2 given with Mesna every other day for three doses.