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
PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy following
radiation therapy in treating patients who have malignant glioma.
- 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.
- Histologically confirmed malignant glioma
- High-grade glioma
- Anaplastic astrocytoma
- Anaplastic mixed oligoastrocytoma
- Anaplastic oligodendroglioma
- Anaplastic ependymoma
- Must have completed radiotherapy
- 18 and over
- Karnofsky 60-100%
- More than 3 months
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Hemoglobin at least 10 g/dL
- 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
- BUN less than 1.5 times ULN
- Creatinine less than 1.5 times ULN
- Pulmonary function test with diffusion greater than 50 OR
- Clearance by the pulmonary service
- 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:
- No prior immunotherapy
- No prior biologic therapy
- No prior chemotherapy
- Not specified
- See Disease Characteristics
- At least 2 weeks since prior radiotherapy
- Not specified