Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This Phase III trial tested the efficacy and safety of intra-arterial 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) for the treatment of newly resected malignant glioma, comparing intra-arterial BCNU and intravenous BCNU (200 mg/sq m every 8 weeks), each regimen without or with intravenous 5-fluorouracil (1 gm/sq m three times daily given 2 weeks after BCNU). All patients also received radiation therapy. A total of 505 patients were randomly assigned within the study. Fifty-seven patients were excluded, primarily because of neuropathology error, and the remaining 448 patients constituted the Valid Study Group. Of the total 505 patients, 190 patients could not receive intra-arterial BCNU and 315 patients were randomly assigned to receive intra-arterial (167 patients) and intravenous (148 patients) BCNU. Actuarial analysis (log-rank) demonstrated reduced survival for the intra-arterial group (p = 0.03). Serious toxicity was observed in the intra-arterial group; 16 patients (9.5%) developed irreversible encephalopathy with computerized tomography evidence of cerebral edema, and 26 patients (15.5%) developed visual loss ipsilateral to the infused carotid artery. Administration of 5-fluorouracil did not influence survival. The survival rate between the intravenous and the intra-arterial BCNU patients with glioblastoma multiforme did not differ, but was worse for intra-arterial BCNU patients with anaplastic astrocytoma than for those receiving intravenous BCNU (p = 0.002). Neuropathologically, intra-arterial BCNU produced white matter necrosis. It is concluded that intra-arterial BCNU is neither safe nor effective in prolonging survival when administered by the methods used in this study of newly diagnosed patients with malignant glioma.
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PMID:A randomized comparison of intra-arterial versus intravenous BCNU, with or without intravenous 5-fluorouracil, for newly diagnosed patients with malignant glioma. 156 40

We describe the neuropathologic findings at autopsy in six patients who developed a progressive encephalopathy complicating the treatment of malignant gliomas with combined intra-arterial 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and cerebral irradiation. Four brains were free of tumor and one contained a microscopic focus of residual glioma. In only one case was there evidence of tumor progression. A disseminated process characterized by miliary foci of necrosis with mineralizing axonopathy was present in all cases, restricted to the internal carotid distribution of the perfused hemisphere and involving primarily though not exclusively the white matter, which was diffusely and severely edematous. This was combined in 3 cases with a histologically dissimilar, massive necrotizing leukoencephalopathy indistinguishable from pure radionecrosis. Much of the toxicity of this therapy is mediated by vascular injury, but the disseminated necrotizing lesion probably reflects, at least in part, direct neural damage.
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PMID:Fatal necrotizing encephalopathy complicating treatment of malignant gliomas with intra-arterial BCNU and irradiation: a pathological study. 182 43

The purpose of this study was to describe acute encephalopathy as a new toxicity associated with paclitaxel, when it is delivered at high doses (> or =600 mg/m2) with stem cell support. A total of 129 patients, included in clinical trials of paclitaxel-containing high-dose chemotherapy, were analyzed. A total of 114 patients received paclitaxel at a dose of > or =600 mg/m2. Six patients presented acute encephalopathy starting between 7 and 23 days after paclitaxel treatment; two of them had received prior whole-brain irradiation. Paclitaxel was given alone (one patient), with cyclophosphamide and cisplatin (two patients), and with cyclophosphamide and cisplatin plus 1,3-bis(2-chloroethyl)-1-nitrosourea (three patients). Central nervous system toxicity consisted of rapid obtundation and coma (five patients) and severe confusional picture with paranoid ideations (one patient). Brain magnetic resonance imaging showed diffuse white matter atrophy (one patient) or multiple small infarcts (one patient), or it was normal (four patients). Other complementary tests, including cerebrospinal fluid analysis and electroencephalography, were nondiagnostic. An effect from concomitant psychotropic medications or from other organ toxicities was excluded in all patients. Three patients recovered after 8-15 days, either spontaneously (two patients) or after high-dose steroids (one patient). Three patients died of irreversible coma. Necropsy, performed in two patients, showed generalized white matter atrophy and multiple brain parenchymal infarcts, respectively. No pharmacodynamic correlation between the occurrence of encephalopathy and a pharmacokinetic parameter of paclitaxel could be identified. Paclitaxel-containing high-dose chemotherapy can cause severe acute encephalopathy. An aggravating effect from prior brain irradiation or concurrent 1,3-bis(2-chloroethyl)-1-nitrosourea seems possible.
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PMID:Acute encephalopathy: a new toxicity associated with high-dose paclitaxel. 1010 Jun 96