Combination Chemotherapy Following Radiation Therapy in Treating Patients With Malignant Glioma
Combination Chemotherapy Following Radiation Therapy in Treating Patients With Malignant Glioma
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
 they stop growing or die. Combining more than one chemotherapy drug may kill more tumor
 cells.

 PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy following
 radiation therapy in treating patients who have 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