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