• Tumor response positive or negative for sodium thiosulfate (STS) as measured by radiographic response from the first day of treatment until tumor progression [ Designated as safety issue: No ]
• Effect of STS on granulocytes and erythrocytes as measured by complete blood count lab values obtained weekly during treatment [ Designated as safety issue: No ]
• Hearing changes assessed by audiology hearing test every 2 months during treatment [ Designated as safety issue: No ]
• Quality of life assessed by EORTC QOL before treatment, at 6 months, and at completion of treatment [ Designated as safety issue: No ]

• Tumor response positive or negative for sodium thiosulfate (STS) as measured by radiographic response from the first day of treatment until tumor progression
• Effect of STS on granulocytes and erythrocytes as measured by complete blood count lab values obtained weekly during treatment
• Hearing changes assessed by audiology hearing test every 2 months during treatment
• Quality of life assessed by EORTC QOL before treatment, at 6 months, and at completion of treatment

RATIONALE: Drugs used in chemotherapy, such as carboplatin, cyclophosphamide, etoposide, and etoposide phosphate, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug (combination chemotherapy) and giving them in different ways may kill more tumor cells. Chemoprotective drugs, such as sodium thiosulfate, may protect blood platelets from the side effects of chemotherapy.

PURPOSE: This randomized phase II trial is studying combination chemotherapy and sodium thiosulfate to see how well they work compared to combination chemotherapy alone in treating patients with high-grade glioma.

OBJECTIVES:

Primary

• Determine the effect of delayed administration of high-dose sodium thiosulfate on platelet counts in patients with high-grade glioma undergoing treatment with intra-arterial carboplatin, cyclophosphamide, and etoposide or etoposide phosphate.

Secondary

• Determine the effect of delayed administration of high-dose sodium thiosulfate on granulocyte and erythrocyte counts in patients treated with this chemotherapy regimen.
• Determine the tumor response in patients treated with this chemotherapy regimen with or without delayed high-dose sodium thiosulfate.
• Determine hearing changes at higher frequencies in the standard testing range (i.e., 4,000 and 8,000 Hz) and at higher frequencies above standard testing range (i.e., 9,000 and 16,000 Hz) in patients treated with these regimens.
• Determine the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to histology type (glioblastoma multiforme vs other high-grade glioma). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive cyclophosphamide IV over 10 minutes, etoposide phosphate IV over 10 minutes (or etoposide IV), and carboplatin intra-arterially over 10 minutes on day 1. Beginning on day 3, patients receive filgrastim (G-CSF) subcutaneously once daily for 7-10 days until blood counts recover.
• Arm II: Patients receive cyclophosphamide, etoposide phosphate or etoposide, carboplatin, and G-CSF as in arm I. At 4 and 8 hours after carboplatin administration, patients receive high-dose sodium thiosulfate IV over 15 minutes.

In both arms, treatment repeats every 4 weeks for 12 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, every 6 months during study treatment, and then within 30 days after the final study treatment.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 60 patients (30 per treatment arm) will be accrued for this study.

• Brain and Central Nervous System Tumors
• Thrombocytopenia

• Drug: carboplatin
• Drug: cyclophosphamide
• Drug: etoposide
• Drug: etoposide phosphate
• Drug: sodium thiosulfate

• Active Comparator: Patients receive cyclophosphamide IV over 10 minutes, etoposide phosphate IV over 10 minutes (or etoposide IV), and carboplatin intra-arterially over 10 minutes on day 1.
• Experimental: Patients receive cyclophosphamide, etoposide phosphate or etoposide, and carboplatin as in arm I. At 4 and 8 hours after carboplatin administration, patients receive high-dose sodium thiosulfate IV over 15 minutes.

DISEASE CHARACTERISTICS:

• Histologically confirmed high-grade glioma by needle biopsy, open biopsy, or surgical resection
• No rapidly progressing CNS disease with associated neurological deterioration

PATIENT CHARACTERISTICS:

Age

• 18 to 75

Performance status

• ECOG 0-2 OR
• Karnofsky 50-100%

Life expectancy

• Not specified

Hematopoietic

• WBC at least 2,500/mm^3
• Absolute granulocyte count at least 1,200/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin less than 2.0 mg/dL
• SGOT/SGPT less than 2.5 times upper limit of normal

Renal

• Creatinine less than 1.8 mg/dL

Cardiovascular

• Adequate cardiovascular function to tolerate monitored anesthesia

Pulmonary

• Adequate pulmonary function to tolerate monitored anesthesia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception for at least 2 months before and during study participation
• No uncontrolled clinically significant confounding medical condition within the past 30 days
• No contraindication to the study medications

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• At least 4 weeks since prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• At least 2 weeks since prior focal or systemic radiotherapy

Surgery

• Prior surgery or biopsy allowed