temozolomide plus lomustine followed by radiation therapy in treating patients with high-grade malignant glioma

Conditions: Brain Tumor; Central Nervous System Tumor

Summary: rationale: drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. radiation therapy uses high-energy x-rays to damage tumor cells. combining more than one chemotherapy drug with radiation therapy may kill more tumor cells. purpose: phase i trial to study the effectiveness of temozolomide plus lomustine followed by radiation therapy in treating patients who have high-grade malignant glioma.

objectives: * determine the maximum tolerated dose of temozolomide when administered with lomustine in patients with high-grade malignant gliomas. * determine the dose-limiting toxic effects of this regimen in these patients. * evaluate the feasibility of radiotherapy after this treatment regimen in this patient population. * evaluate the radiographic responses in patients treated with this regimen. outline: this is a multicenter, dose-escalation study of temozolomide. patients receive oral temozolomide on days 1-5 and oral lomustine on day 1. treatment continues every 28 days, if blood counts have recovered, for 2 courses in the absence of disease progression or unacceptable toxicity. patients then undergo radiotherapy on days 1-5 weekly for 6 weeks. patients continue the same chemotherapy regimen for up to 6 more courses beginning 4 weeks after completion of radiotherapy. 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 3 or 2 of 6 patients experience dose-limiting toxicity. patients are followed for survival. projected accrual: a total of 3-30 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically confirmed high-grade malignant glioma of one of the following subtypes: * glioblastoma * anaplastic astrocytoma * anaplastic oligoastrocytoma * gliomatosis cerebri * no disseminated disease or primary spinal cord malignancies * measurable intracranial residual disease by mri patient characteristics: age: * 3 and over * under 22 at time of diagnosis performance status: * karnofsky 50-100% if over 10 years of age * lansky 50-100% if 10 years of age or under life expectancy: * at least 8 weeks hematopoietic: * absolute neutrophil count at least 1,000/mm\^3 * platelet count at least 100,000/mm\^3 (transfusion independent) * hemoglobin at least 8.0 g/dl (rbc transfusions allowed) hepatic: * bilirubin no greater than 1.5 times normal for age * sgpt no greater than 2.5 times normal for age * albumin at least 2 g/dl renal: * creatinine no greater than 1.5 times normal for age or * creatinine clearance or radioisotope glomerular filtration rate at least lower limit of normal for age pulmonary: * no dyspnea at rest * no exercise intolerance * pulse oximetry at least 94% other: * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * no uncontrolled infection prior concurrent therapy: biologic therapy: * no prior biologic therapy * no concurrent prophylactic hematopoietic growth factors chemotherapy: * no prior chemotherapy endocrine therapy: * prior corticosteroid therapy allowed * no concurrent corticosteroids as antiemetic radiotherapy: * no prior radiotherapy surgery: * no more than 31 days since prior maximal neurosurgical procedure other: * no concurrent phenobarbital or cimetidine

Keywords: childhood high-grade cerebral astrocytoma