RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. O6-benzylguanine may help carmustine kill more tumor cells by making tumor cells more sensitive to the drug. It is not yet known whether radiation therapy and carmustine are more effective with or without O6-benzylguanine.

PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy plus carmustine with or without O6-benzylguanine in treating patients who have newly diagnosed glioblastoma multiforme or gliosarcoma.

OBJECTIVES:

• Compare the overall survival, failure-free survival, and progression-free survival of patients with newly diagnosed glioblastoma multiforme or gliosarcoma treated with radiotherapy and carmustine with or without O6-benzylguanine.
• Compare the frequency and severity of toxic effects of these regimens in these patients.
• Correlate the survival of these patients with the expression of O6-alkylguanine-DNA alkyltransferase.

OUTLINE: This is a randomized study. Patients are stratified according to age (under 50 vs 50 and over), prior surgery (biopsy only vs resection), and Zubrod performance status (0-1 vs 2). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo radiotherapy daily 5 days a week over 7 weeks for a total of 34 fractions. Patients also receive chemotherapy comprising O6-benzylguanine IV over 1 hour followed 6 hours later by carmustine IV over 1 hour on day 1 of radiotherapy. Chemotherapy repeats every 6 weeks for a maximum of 7 courses in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients undergo radiotherapy as in arm I. Patients receive carmustine IV as in arm I.

Patients are followed at week 48, every 4 months for 1 year, and then every 6 months for 4 years.

PROJECTED ACCRUAL: A total of 375 patients will be accrued for this study within 5 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed glioblastoma multiforme or gliosarcoma

  • Biopsy or surgical resection within the past 28 days

    • MRI* with gadolinium performed before registration
    • Patients who undergo a simple biopsy only require preoperative MRI* with gadolinium

• No more than 2 noncontiguous tumor sites based on T2-weighted MRI (in 3 dimensions)*

• No prior radiotherapy-delivered cephalad to the interspace between the seventh cervical and the first thoracic vertebral body NOTE: *If an MRI is not medically feasible, patients may have a CT scan with contrast

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Zubrod 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 3,000/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 8 g/dL

Hepatic:

• Bilirubin no greater than 2 times upper limit of normal (ULN)
• SGOT/SGPT no greater than 2 times ULN
• Alkaline phosphatase no greater than 2 times ULN
• PT/PTT no greater than 1.2 times ULN

Renal:

• Not specified

Cardiac:

• No severe cardiac disease, including any of the following:

  • Uncontrolled arrhythmias or conduction defects
  • Major problems with edema (e.g., residual swelling in the legs from deep vein thrombosis)
  • Recent coronary artery disease
  • Poorly controlled hypertension (i.e., diastolic blood pressure greater than 110 mm Hg and/or systolic blood pressure greater than 180 mm Hg)

Pulmonary:

• DLCO at least 70% of predicted
• No severe pulmonary disease

Other:

• HIV negative
• No severe Cushing's syndrome
• No known allergies to any of the study drugs
• No major psychiatric illness
• No poorly controlled diabetes complicated by steroid treatment
• No other medical illness that cannot be adequately controlled or that would preclude study participation
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy
• No other concurrent antitumor chemotherapy

Endocrine therapy:

• No concurrent hormonal therapy except postmenopausal estrogen replacement therapy
• Corticosteroids at stable or decreasing dose for tumor edema allowed

Radiotherapy:

• See Disease Characteristics
• No prior radiotherapy
• No other concurrent radiotherapy (including intensity-modulated radiotherapy) to the index lesion(s)

Surgery:

• See Disease Characteristics
• No concurrent antitumor surgery

Other:

• No other concurrent investigational drugs
• No other concurrent antineoplastic drugs or therapy