Combination Chemotherapy Following Radiation Therapy in Treating Patients With Malignant Glioma

OBJECTIVES:

• Determine the safety and efficacy of extended low-dose temozolomide when combined with carmustine after radiotherapy in patients with malignant glioma.
• Determine the maximum tolerated dose of this combination in this patient population.
• Determine time to progression as measured from baseline gadolinium-enhanced magnetic resonance imaging in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of temozolomide.

Patients receive oral temozolomide once daily on days 1-28 and carmustine IV over 1-3 hours beginning within 72 hours after starting temozolomide. Courses repeat every 8 weeks for up to 1 year in the absence of unacceptable toxicity or disease progression.

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

Patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 3-24 patients will be accrued for this study within 1-2 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant glioma

• Glioblastoma
• Gliosarcoma
• High-grade glioma
• Anaplastic astrocytoma
• Anaplastic mixed oligoastrocytoma
• Anaplastic oligodendroglioma
• Anaplastic ependymoma
• Must have completed radiotherapy

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• More than 3 months

Hematopoietic:

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

Hepatic:

• Bilirubin less than 1.5 times upper limit of normal (ULN)
• SGOT/SGPT less than 3 times ULN
• Alkaline phosphatase less than 2 times ULN

Renal:

• BUN less than 1.5 times ULN
• Creatinine less than 1.5 times ULN

Pulmonary:

• Pulmonary function test with diffusion greater than 50 OR
• Clearance by the pulmonary service

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No AIDS-related illness
• No nonmalignant systemic disease that would preclude study
• No acute infection requiring IV antibiotics
• No psychiatric condition that would preclude study compliance
• No frequent vomiting or medical condition that would interfere with oral medication intake (e.g., partial bowel obstruction)
• No other prior or concurrent malignancy except surgically cured carcinoma in situ of the cervix or basal cell or squamous cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior immunotherapy
• No prior biologic therapy

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• At least 2 weeks since prior radiotherapy

Surgery:

• Not specified