Acetylcysteine, Mannitol, Combination Chemotherapy, and Sodium Thiosulfate in Treating Children With Malignant Brain Tumors

OBJECTIVES: Primary * Determine the toxicity and maximum tolerated dose of acetylcysteine when given in combination with blood-brain barrier disruption treatment with mannitol, combination chemotherapy comprising cyclophosphamide, etoposide phosphate, and carboplatin, and delayed high-dose sodium thiosulfate in pediatric patients with malignant brain tumors. Secondary * Determine the blood/bone marrow toxicity of this regimen in these patients. * Determine tumor response in patients treated with this regimen. OUTLINE: This is a dose-escalation study of acetylcysteine. Patients receive acetylcysteine IV over 30-60 minutes followed, at least 15 minutes later, by x-ray-guided femoral artery catheterization under general anesthesia on days 1 and 2. After placement of the catheter, patients receive cyclophosphamide IV over 10 minutes, etoposide phosphate IV over 10 minutes, mannitol intra-arterially (IA) over 30 seconds, and carboplatin IA over 10 minutes also on days 1 and 2. Patients then receive high-dose sodium thiosulfate IV over 15 minutes 4 hours after completion of carboplatin. Some patients may receive a second dose of sodium thiosulfate 8 hours after completion of carboplatin. Beginning 48 hours after the last dose of chemotherapy on day 2, patients receive filgrastim (G-CSF) subcutaneously once daily for 7-10 days or until blood counts recover. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of acetylcysteine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. An additional 3 patients are treated at the MTD. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.