Temozolomide and Carmustine in Treating Patients With Anaplastic Glioma
Temozolomide and Carmustine in Treating Patients With Anaplastic 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 drug may kill more tumor cells.

 PURPOSE: Phase II trial to study the effectiveness of 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