RATIONALE: Biological therapies such as gefitinib may interfere with the growth of the tumor cells and slow the growth of the tumor. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining gefitinib with radiation therapy may kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of combining gefitinib with radiation therapy in treating patients who have glioblastoma multiforme.

OBJECTIVES:

• Determine the maximum tolerated dose of gefitinib when given concurrently with cranial radiotherapy in patients with glioblastoma multiforme.
• Determine the overall survival and progression-free survival of patients treated with this regimen.
• Determine the feasibility and toxicity of this regimen in these patients.

OUTLINE: This is a multicenter, dose-escalation study of gefitinib. Patients are stratified according to whether they are concurrently receiving enzyme-inducing anticonvulsant drugs (EIACD) (yes vs no).

• Phase I:Patients receive oral gefitinib once daily for 7 weeks. Beginning 1 week after initiation of gefitinib, patients undergo cranial radiotherapy once daily 5 days a week for 6 weeks. After the completion of radiotherapy, patients continue to receive oral gefitinib once daily for 18 months in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of gefitinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

• Phase II:Patient receive oral gefitinib at the MTD as in phase I. Patients undergo cranial radiotherapy as in phase I.

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

PROJECTED ACCRUAL: A total of 30 patients (18 enzyme-inducing anticonvulsant drug [EIACD] patients and 12 non-EIACD patients) will be accrued for phase I of this study within 2 months. A maximum of 140 patients will be accrued for phase II of this study within 10 months.

• Drug: gefitinib
• Radiation: radiation therapy

DISEASE CHARACTERISTICS:

• Histologically confirmed glioblastoma multiforme with areas of necrosis

  • Tumor must be supratentorial
• Diagnosis made by surgical biopsy or excision
• No recurrent or multifocal disease
• No metastases detected below the tentorium or beyond the cranial vault
• Tumor tissue and serum samples required

PATIENT CHARACTERISTICS:

Age:

• Adult

Performance status:

• Zubrod 0-1

Life expectancy:

• At least 8 weeks

Hematopoietic:

• Hemoglobin at least 10 g/dL (transfusions allowed)
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 2.0 mg/dL
• SGPT or SGOT no greater than 2 times normal

Renal:

• Creatinine no greater than 1.5 mg/dL
• BUN no greater than 25 mg/dL

Other:

• No known AIDS
• No other major medical illness or psychiatric impairment that would preclude study participation
• No active connective tissue disorders, including lupus and scleroderma
• No known multiple sclerosis
• No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix or bladder
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy or radiosensitizers for cancers of the head and neck

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy to the head and neck except for T1 glottic tumors

Surgery:

• See Disease Characteristics
• No more than 5 weeks since prior surgery and recovered
• No concurrent ophthalmic surgery

Other:

• At least 30 days since prior participation in another clinical study
• No concurrent participation in another clinical study
• No concurrent systemic retinoids or herbal medicines
• No concurrent drugs that induce CytP4503A4 except enzyme-inducing anticonvulsant drugs