S0001 RT and Carmustine With or Without O6BG in Patients With New 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