procarbazine in treating patients with recurrent brain tumor

Conditions: Brain and Central Nervous System Tumors

Summary: rationale: drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. purpose: phase i/ii trial to study the effectiveness of procarbazine in treating patients who have progressive or recurrent astrocytoma, oligodendroglioma, or glioblastoma multiforme following treatment with radiation therapy.

objectives: * determine the maximum tolerated dose of oral procarbazine when administered to patients with recurrent glioma receiving or not receiving anticonvulsants metabolized by the p450 hepatic enzyme complex. * determine the pharmacokinetics of oral procarbazine, including any effects of hepatic enzyme inducing drugs, in these patients. * assess the response rate to procarbazine in these patients. * evaluate this regimen in terms of overall survival and duration of disease free survival in these patients. * evaluate the toxicity of this regimen in these patients. outline: phase i of this study is a dose escalation study. patients are stratified according to concurrent use of anticonvulsant drugs that induce cytochrome p450 (yes vs no drugs or modest-induction drugs). * phase i: patients receive oral procarbazine once daily for 5 days. treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. cohorts of 6 patients receive escalating doses of oral procarbazine until the maximum tolerated dose (mtd) is determined. * phase ii: once the mtd is determined, patients receive procarbazine as in phase i. patients are followed every 2 months until death. projected accrual: a total of 24-35 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically proven malignant glioma of one of the following types: * anaplastic astrocytoma * anaplastic oligodendroglioma * glioblastoma multiforme * progressive or recurrent disease after radiotherapy with or without chemotherapy * measurable disease by serial mr or ct patient characteristics: age: * 18 and over performance status: * karnofsky 60-100% life expectancy: * greater than 2 months hematopoietic: * absolute neutrophil count at least 1500/mm\^3 * platelet count at least 100,000/mm\^3 hepatic: * bilirubin no greater than 1.5 mg/dl * sgpt/sgot no greater than 4 times upper limit of normal renal: * creatinine no greater than 1.7 mg/dl other: * no serious concurrent infection * no other illness that would preclude study * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * no prior malignancy within the past 5 years except curatively treated basal cell skin cancer or carcinoma in situ of the cervix prior concurrent therapy: biologic therapy: * no concurrent filgrastim (g-csf) during the first course chemotherapy: * see disease characteristics * no more than 1 prior chemotherapy regimen * at least 3 weeks since prior chemotherapy (at least 6 weeks since prior nitrosoureas) * no more than 2 prior courses of carmustine or lomustine and no greater than 460 mg/m2 or 220 mg/m2, respectively * no prior procarbazine endocrine therapy: * not specified radiotherapy: * see disease characteristics * at least 3 months since prior radiotherapy surgery: * prior surgery allowed other: * recovered from toxicity of prior therapy * at least 10 days since prior anticonvulsants for patients in arm ii * no concurrent investigational agents * no concurrent ethanol, ephedrine, isoproterenol, epinephrine, tricyclic antidepressants, paragyliline, narcotic analgesics, antihistamines, phenothiazines, hypotensives, or barbiturates * at least 14 days since prior antidepressants (e.g., ssri and/or mao inhibitor) * must avoid foods high in tyramine (i.e., dark beer, wine, yogurt, cheese, bananas)

Keywords: recurrent adult brain tumor adult glioblastoma adult anaplastic astrocytoma adult anaplastic oligodendroglioma adult giant cell glioblastoma adult gliosarcoma