Computer Planned Radiation Therapy Plus Chemotherapy in Treating Patients With Glioblastoma Multiforme

OBJECTIVES:

• Determine the feasibility and toxicity of escalating doses of conformal radiotherapy planned with 3-D treatment planning plus carmustine in patients with glioblastoma multiforme.
• Determine dose/volume and dose/anatomic characteristics that influence radiotherapy-induced CNS (central nervous system) toxicity.
• Evaluate local control, survival, and failure patterns of these patients treated with high doses of conformal radiotherapy to gross disease.
• Correlate changes on cross-sectional diagnostic MRI imaging studies to clinical or biologic endpoints.

OUTLINE: This is a dose-escalation study. Patients are stratified according to the planned target volume, i.e., gross residual tumor plus 3 mm (less than 75 cc vs at least 75 cc).

Patients undergo radiotherapy over 15-30 minutes daily 5 days a week for 6-8 weeks. After 46 Gy of radiotherapy have been administered, patients undergo radiotherapy field reduction and are accrued into one of four dose levels. (Dose level 1 closed to accrual 1/16/01) All patients receive at least 33 radiation treatments. Each patient is evaluated for acute dose-limiting toxicity for 90 days from start of therapy.

Patients also receive carmustine IV over 1-2 hours daily on days 1-3 for the first week of radiotherapy. Treatment repeats every 8 weeks for up to 6 courses.

Patients are followed every 4 months for 2 years, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 40 patients (20 per arm) will be accrued for this study within at least 5 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed glioblastoma multiforme with areas of necrosis as diagnosed by surgical biopsy or subtotal excision

• Supratentorial tumor
• Gross measurable residual disease
• No well-differentiated or anaplastic astrocytoma, multifocal glioma, or recurrent glioblastoma multiforme
• Therapy must begin within 5 weeks after surgery but within 1 week after registration
• CT or MRI scan preoperatively and MRI postoperatively prior to initiation of radiotherapy

• If undergoing a stereotactic-guided needle biopsy, not required to repeat MRI after procedure if the prebiopsy MRI is suitable for treatment planning
• Prior complete surgical resection of tumor allowed

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9 g/dL

Hepatic:

• Bilirubin no greater than 2 mg/dL
• SGPT (serum glutamate pyruvate transaminase) or SGOT (serum glutamic oxaloacetic transaminase) no greater than 2 times normal

Renal:

• BUN (blood urea nitrogen) no greater than 30 mg/dL
• Creatinine no greater than 1.8 mg/dL

Pulmonary:

• Normal chest x-ray OR
• DLCO (carbon monoxide diffusing capacity) at least 60% predicted

Other:

• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except carcinoma in situ of the cervix or bladder, ductal carcinoma in situ of the breast, or nonmelanomatous skin cancer
• Neurologic functional status 0-3
• No major medical illness or psychiatric impairments that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior systemic chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy to head or neck

Surgery:

• See Disease Characteristics