Temozolomide and Carmustine in Treating Patients With Anaplastic Glioma

OBJECTIVES: I. Evaluate the activity, measured in terms of progression free survival, of
carmustine plus temozolomide in recurrent glioblastoma. II. Estimate the response rate of
recurrent glioblastomas to this combination. III. Estimate the response rate of newly
diagnosed anaplastic astrocytomas and mixed anaplastic glioma to this combination. IV.
Evaluate the qualitative and quantitative toxicities of this combination in patients with
anaplastic gliomas.

OUTLINE: This is a nonrandomized study. Patients are stratified by disease (recurrent
glioblastoma vs anaplastic astrocytoma or mixed anaplastic glioma). Patients receive
carmustine intravenously on day 1 two hours prior to temozolomide. Temozolomide is
administered orally on day 1. Cycles repeat every 42 days. Treatment for patients with
recurrent glioblastoma may continue for 8 cycles in the absence of disease progression or
unacceptable toxicity. If there is no disease progression after 8 cycles, treatment may
continue further at the investigator's discretion. Patients with anaplastic astrocytoma or
mixed anaplastic glioma continue for 4 cycles of treatment. Patients are followed
periodically at the investigator's discretion, at least twice in the first 4 months, and then
until death.

PROJECTED ACCRUAL: A minimum of 17 patients and a maximum of 37 patients will be accrued in
the recurrent glioblastoma stratum and 45 patients will be accrued into the anaplastic
astrocytoma and mixed anaplastic glioma stratum.

DISEASE CHARACTERISTICS: Histologically confirmed malignant glioma - Recurrent glioblastoma
- Anaplastic astrocytoma - Mixed anaplastic glioma For recurrent glioblastoma: Required
documented progression must include an increase in tumor size of at least 25% or appearance
of new lesion For anaplastic astrocytoma or mixed anaplastic glioma: Must have measurable,
contrast enhancing disease on postoperative CT or MRI scan No postoperative radiation or
chemotherapy If patients have received prior brachytherapy or stereotactic radiosurgery,
they must have confirmation of true progressive disease rather than radiation necrosis by
PET scanning or biopsy

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life
expectancy: Not specified Hematopoietic: WBC at least 3,500/mm3 Absolute neutrophil count
at least 1,800/mm3 Platelet count at least 125,000/mm3 Hemoglobin at least 9 g/dL
(transfusion allowed) Hepatic: Bilirubin less than 1.5 mg/dL SGOT less than 2.0 times upper
limit of normal Renal: Creatinine less than 1.5 mg/dL OR Creatinine clearance greater than
70 mL/min Cardiovascular: No uncontrolled arrhythmias or conduction defects No unstable or
newly diagnosed angina pectoris No New York Heart Association class II-IV heart disease No
congestive heart failure No major problems with edema (e.g., severe Cushing's syndrome,
residual leg swelling from deep-vein thrombosis) No recent coronary artery disease No
poorly controlled hypertension (diastolic greater than 110 mmHg and systolic greater than
180 mmHg) Pulmonary: DLCO greater than 80% of expected value Other: HIV negative No major
psychiatric illness No other prior malignancy except adequately treated basal cell or
squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer
from which the patient is currently in complete remission, or any other cancer from which
the patient has been free of disease for 5 years Not pregnant or nursing Adequate
contraception required of all fertile patients

PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent biologic therapy Chemotherapy: No
prior nitrosourea or temozolomide No more than 1 prior chemotherapy regimen allowed for
patients with glioblastoma At least 6 weeks since mitomycin or procarbazine and recovered
At least 4 weeks since other prior chemotherapy and recovered No other concurrent
chemotherapy Endocrine therapy: If receiving steroids, must be on a stable steroid dose for
at least 72 hours prior to study No other concurrent endocrine therapy Radiotherapy: At
least 6 weeks since radiotherapy No greater than 10-20% of marrow irradiated in prior
radiotherapy No other concurrent radiotherapy Surgery: Surgery allowed