The objectives of this study are: 1) to determine the toxicity and maximum tolerated dose of hydroxyurea (HU) in a 24-hr infusion given concurrently with BCNU; 2) to estimate the response rate of patients with anaplastic gliomas to combination therapy with HU and BCNU. Adult patients will be eligible if they have pathologically proven glioblastoma multiforme, anaplastic astrocytoma or other anaplastic glioma, and have measurable disease on contrast-enhanced CT or MR scan. Patients will be stratified into two groups: Group A with newly diagnosed anaplastic gliomas who have undergone stereotactic biopsy only (no other treatment); and Group B who have undergone biopsy or resection followed by cranial radiotherapy. In each treatment cycle patients will receive IV BCNU 200 mg/m2 and an IV loading dose of HU followed by a continuous 24-hr HU infusion. The loading and infusion doses of HU will be escalated (separately in Groups A and B) in groups of at least 3 patients per dose level; additional patients will be added and the dose escalation schedule will be modified as dictated by neurologic or systemic toxicity. Patients will receive ganulocyte colony stimulating factor (GCSF) as needed in an effort to ameliorate myelosuppression. Treatment cycles will be repeated every 6 weeks. Therapeutic efficacy will be determined by a standard combination of serial neurologic examinations and quantitative measurements of tumor size on CT or MR scans.
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