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      Posterior reversible encephalopathy syndrome (PRES) induced by pazopanib, a multi-targeting tyrosine kinase inhibitor, in a patient with soft-tissue sarcoma: case report and review of the literature

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          Summary

          Posterior reversible encephalopathy syndrome (PRES) is a clinical entity characterized by acute neurological symptoms such as severe headache, seizures, and visual disturbance, and by typical reversible lesion on brain magnetic resonance (MR) images. Since PRES is thought to be caused by vascular endothelial injury due to cytotoxic agents or acute systemic hypertension, the number of reports on PRES associated with angiogenesis inhibitors has been increasing. Although five cases that developed PRES due to pazopanib for renal cell carcinoma have already been reported, none of PRES due to pazopanib for soft-tissue sarcoma has been reported thus far. We describe a case of a 49-year-old woman with retroperitoneal soft-tissue sarcoma who developed PRES during pazopanib administration. Pazopanib at 800 mg/day was administered as her third-line treatment at relapse. After 38 days of pazopanib, she was admitted to our hospital with severe headache, vomiting, and systemic hypertension. The next day, she developed consciousness deterioration and visual disturbance together with exacerbated systemic hypertension. Brain MR images revealed hyper-intense signals on FLAIR sequences in the bilateral occipital lobes and the left thalamus. Intravenous nicardipine injection was immediately started to control her blood pressure and pazopanib was discontinued. Her symptoms gradually improved and disappeared on the fifth hospital day. After 2 weeks, hyper-intense signals on a FLAIR sequence disappeared completely. She restarted a low dose of pazopanib under good blood pressure control and experienced no subsequent recurrence of PRES.

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          Most cited references16

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          2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

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            Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial.

            Pazopanib, a multitargeted tyrosine kinase inhibitor, has single-agent activity in patients with advanced non-adipocytic soft-tissue sarcoma. We investigated the effect of pazopanib on progression-free survival in patients with metastatic non-adipocytic soft-tissue sarcoma after failure of standard chemotherapy. This phase 3 study was done in 72 institutions, across 13 countries. Patients with angiogenesis inhibitor-naive, metastatic soft-tissue sarcoma, progressing despite previous standard chemotherapy, were randomly assigned by an interactive voice randomisation system in a 2:1 ratio in permuted blocks (with block sizes of six) to receive either pazopanib 800 mg once daily or placebo, with no subsequent cross-over. Patients, investigators who gave the treatment, those assessing outcomes, and those who did the analysis were masked to the allocation. The primary endpoint was progression-free survival. Efficacy analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00753688. 372 patients were registered and 369 were randomly assigned to receive pazopanib (n=246) or placebo (n=123). Median progression-free survival was 4·6 months (95% CI 3·7-4·8) for pazopanib compared with 1·6 months (0·9-1·8) for placebo (hazard ratio [HR] 0·31, 95% CI 0·24-0·40; p<0·0001). Overall survival was 12·5 months (10·6-14·8) with pazopanib versus 10·7 months (8·7-12·8) with placebo (HR 0·86, 0·67-1·11; p=0·25). The most common adverse events were fatigue (60 in the placebo group [49%] vs 155 in the pazopanib group [65%]), diarrhoea (20 [16%] vs 138 [58%]), nausea (34 [28%] vs 129 [54%]), weight loss (25 [20%] vs 115 [48%]), and hypertension (8 [7%] vs 99 [41%]). The median relative dose intensity was 100% for placebo and 96% for pazopanib. Pazopanib is a new treatment option for patients with metastatic non-adipocytic soft-tissue sarcoma after previous chemotherapy. GlaxoSmithKline. Copyright © 2012 Elsevier Ltd. All rights reserved.
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              A reversible posterior leukoencephalopathy syndrome.

              In some patients who are hospitalized for acute illness, we have noted a reversible syndrome of headache, altered mental functioning, seizures, and loss of vision associated with findings indicating predominantly posterior leukoencephalopathy on imaging studies. To elucidate this syndrome, we searched the log books listing computed tomographic (CT) and magnetic resonance imaging (MRI) studies performed at the New England Medical Center in Boston and Hôpital Sainte Anne in Paris; we found 15 such patients who were evaluated from 1988 through 1994. Of the 15 patients, 7 were receiving immunosuppressive therapy after transplantation or as treatment for aplastic anemia, 1 was receiving interferon for melanoma, 3 had eclampsia, and 4 had acute hypertensive encephalopathy associated with renal disease (2 with lupus nephritis, 1 with acute glomerulonephritis, and 1 with acetaminophen-induced hepatorenal failure). Altogether, 12 patients had abrupt increases in blood pressure, and 8 had some impairment of renal function. The clinical findings included headaches, vomiting, confusion, seizures, cortical blindness and other visual abnormalities, and motor signs. CT and MRI studies showed extensive bilateral white-matter abnormalities suggestive of edema in the posterior regions of the cerebral hemispheres, but the changes often involved other cerebral areas, the brain stem, or the cerebellum. The patients were treated with antihypertensive medications, and immunosuppressive therapy was withdrawn or the dose was reduced. In all 15 patients, the neurologic deficits resolved within two weeks. Reversible, predominantly posterior leukoencephalopathy may develop in patients who have renal insufficiency or hypertension or who are immunosuppressed. The findings on neuroimaging are characteristic of subcortical edema without infarction.
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                Author and article information

                Contributors
                +81-55-989-5222 , k.mitsuya@scchr.jp
                Journal
                Invest New Drugs
                Invest New Drugs
                Investigational New Drugs
                Springer US (New York )
                0167-6997
                1573-0646
                25 October 2017
                25 October 2017
                2018
                : 36
                : 2
                : 346-349
                Affiliations
                [1 ]ISNI 0000 0004 1774 9501, GRID grid.415797.9, Divisions of Neurosurgery, Shizuoka Cancer Center, ; 1007, Shimo-nagakubo, Naga-izumi, Shizuoka, 411-8777 Japan
                [2 ]ISNI 0000 0004 1774 9501, GRID grid.415797.9, Orthopedic Oncology, Shizuoka Cancer Center, ; Shizuoka, Japan
                [3 ]ISNI 0000 0004 1774 9501, GRID grid.415797.9, Diagnostic Radiology, Shizuoka Cancer Center, ; Shizuoka, Japan
                Author information
                http://orcid.org/0000-0001-8956-5427
                Article
                521
                10.1007/s10637-017-0521-5
                5869870
                29067537
                7d0a44b0-e429-44c2-b788-48aa688c52be
                © The Author(s) 2017

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 7 September 2017
                : 2 October 2017
                Categories
                Short Report
                Custom metadata
                © Springer Science+Business Media, LLC, part of Springer Nature 2018

                Pharmacology & Pharmaceutical medicine
                posterior reversible encephalopathy syndrome,soft-tissue sarcoma,mri,pazopanib

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