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 post-ifosfamide 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.
RCT Entities:
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 post-ifosfamide 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.
Authors: R L Heideman; E C Douglass; J A Langston; J P Krischer; P C Burger; E H Kovnar; L E Kun; H S Friedman; R Kadota Journal: J Neurooncol Date: 1995 Impact factor: 4.130