Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

SU5416 is a novel small molecule tyrosine kinase inhibitor of the VEGF receptors 1 and 2. A phase I dose escalation study stratified by concurrent use (stratum II) or absence (stratum I) of enzyme-inducing anticonvulsant drugs was undertaken to estimate the maximum-tolerated dose (MTD) and to describe the toxicity profile of SU5416 in pediatric patients with refractory brain tumors. Dose escalations were conducted independently for stratum I starting at 110 mg/m(2) while stratum II started at 48 mg/m(2). Thirty-three eligible patients were treated on stratum I (n = 23) and stratum II (n = 10). Tumor types included 23 glial tumors, 4 neural tumors, 4 ependymomas, and 2 choroid plexus carcinomas. The MTD in stratum I was initially estimated to be 110 mg/m(2). The protocol was amended to determine the MTD after excluding transient AST elevation. Re-estimation of the MTD began at the 145 mg/m(2) dose level but due to development of SU5416 being stopped by the sponsor, the trial was closed before completion. The most serious drug-related toxicities were grade 3 liver enzyme abnormalities, arthralgia, and hallucinations. The plasma pharmacokinetics of SU5416 was not significantly affected by the concurrent administration of enzyme-inducing anticonvulsant drugs. Mean values of the total body clearance, apparent volume of distribution, and terminal phase half-life of SU5416 for the 19 patients in stratum I were 26.1 +/- 12.5 l/hr/m(2), 41.9 +/- 21.4 l/m(2), and 1.11 +/- 0.41 hr, respectively. The plasma pharmacokinetics of SU5416 in children was similar to previously reported findings in adult cancer patients. Prolonged disease stabilization was observed in 4 of 16 stratum I patients.
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PMID:Phase I study of SU5416, a small molecule inhibitor of the vascular endothelial growth factor receptor (VEGFR) in refractory pediatric central nervous system tumors. 1906 67

Pleomorphic xanthoastrocytoma (PXA) is a World Health Organization Grade 2 glioma that is uncommon (<1 % all adult gliomas) and seen primarily in children and young adults. PXA has been demonstrated to manifest the V600E BRAF mutation in nearly 70 % of all tumors, a mutation that constitutively activates the BRAF/MEK signaling pathway. Assess response and toxicity of a BRAF inhibitor, vemurafenib, in recurrent PXA manifesting the V600E mutation. Four adults [2 males; 2 female: median age 45 years (range 34-53)] with surgery, radiation and alkylator refractory recurrent PXA demonstrating the BRAF mutation (V600E) were treated with vemurafenib. A cycle of vemurafenib was defined as 4 weeks of continuous therapy. All toxicities seen were grade 2 and included arthralgia, photosensitivity, fatigue and nausea (1 patient each). The median number of cycles of therapy was 5 (range 2-10). Radiographic response was progressive disease in 1, stable disease in 2 and partial response in 1. Median progression free survival was 5 months (range 2-10 months). Median overall survival was 8 months (range 4-14 months). In this small retrospective series of select patients with recurrent PXA manifesting the BRAF V600E activating mutation, vemurafenib appears to have single agent activity with manageable toxicity. Confirmation in a larger series of similar patients is required.
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PMID:Salvage therapy with BRAF inhibitors for recurrent pleomorphic xanthoastrocytoma: a retrospective case series. 2375 28

Diagnosis of multiple sclerosis (MS) is difficult when the lesion mimics glioma or cerebral enchephalitis. We report a case of pediatric MS initially suspected as brain stem glioma. An 11-year-old boy developed left foot joint pain followed by progressive symptoms such as left arm and leg weakness, dysarthria, paraplegia, and decreased level of consciousness. He subsequently developed respiratory distress requiring endotracheal intubation and mechanical ventilation. Magnetic resonance imaging showed a mass measuring 2 cm in the medulla oblongata. Although this mass was initially suspected as a glioma, the patient's acutely progressive disease course was not consistent with this diagnosis. Open biopsy revealed inflammation and demyelination, but no malignant cells were detected. He was treated with steroid pulse therapy, which showed dramatic effects. Nine months later, he developed another episode characterized by several neurological symptoms, and the diagnosis of MS was clinically confirmed. Open brain stem biopsy is technically demanding, but this case demonstrates that appropriate neurosurgical evaluation can play an important role in diagnosis by ruling out glioma and confirming MS.
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PMID:[Diagnostic value of brain biopsy in a pediatric multiple sclerosis mimicking brain stem glioma]. 2381 76