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      OncoTargets and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the pathological basis of cancers, potential targets for therapy and treatment protocols to improve the management of cancer patients. Publishing high-quality, original research on molecular aspects of cancer, including the molecular diagnosis, since 2008. Sign up for email alerts here. 50,877 Monthly downloads/views I 4.345 Impact Factor I 7.0 CiteScore I 0.81 Source Normalized Impact per Paper (SNIP) I 0.811 Scimago Journal & Country Rank (SJR)

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      Prevention and treatment of tumor lysis syndrome, and the efficacy and role of rasburicase

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          Abstract

          Tumor lysis syndrome (TLS) is a potentially life-threatening condition that occurs in oncologic and hematologic patients with large tumor burden, either due to cytotoxic therapy or, less commonly, spontaneously because of massive tumor cell lysis. TLS is clinically characterized by acute renal failure, hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia. While limited options are available for treating TLS, identifying patients at high risk for developing TLS and prevention in high-risk patients remain an important aspect in the treatment of cancer patients. In general, treatment of TLS consists of intensive hydration, stimulation of diuresis, and, more specifically, in the use of allopurinol and rasburicase. Rasburicase, a recombinant urate oxidase, rapidly and effectively reduces hyperuricemia, which subsequently significantly decreases the risk of acute renal failure and other clinical manifestations of TLS. For this review, a comprehensive literature search using the term “tumor lysis syndrome” and/or “rasburicase” was performed considering articles listed in MEDLINE. Incidence, prevention, and therapy of TLS with a special focus on the role of rasburicase are discussed. We evaluated 120 relevant articles including 35 case reports, 32 clinical trials, and 14 meta-analyses.

          Most cited references74

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          Gout therapeutics: new drugs for an old disease.

          The approval of febuxostat, a non-purine-analogue inhibitor of xanthine oxidase, by the European Medicines Agency and the US Food and Drug Administration heralds a new era in the treatment of gout. The use of modified uricases to rapidly reduce serum urate concentrations in patients with otherwise untreatable gout is progressing. Additionally, advances in our understanding of the transport of uric acid in the renal proximal tubule and the inflammatory response to monosodium urate crystals are translating into potential new treatments. In this Review, we focus on the clinical trials of febuxostat. We also review results from studies of pegloticase, a pegylated uricase in development, and we summarise data for several other pipeline drugs for gout, such as the selective uricosuric drug RDEA594 and various interleukin-1 inhibitors. Finally, we issue a word of caution about the proper use of the new drugs and the already available drugs for gout. At a time of important advances, we need to recommit ourselves to a rational approach to the treatment of gout. Copyright © 2011 Elsevier Ltd. All rights reserved.
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            Pathophysiology, clinical consequences, and treatment of tumor lysis syndrome.

            Tumor lysis syndrome is an oncologic emergency that is characterized by severe electrolyte abnormalities and, frequently, by acute renal failure. The syndrome typically occurs in patients with lymphoproliferative malignancies, most often after initiation of treatment. The pathophysiology involves massive tumor cell lysis resulting in the release of large amounts of potassium, phosphate, and uric acid. Deposition of uric acid and calcium phosphate crystals in the renal tubules may lead to acute renal failure, which is often exacerbated by concomitant intravascular volume depletion. The kidney normally excretes these products, and consequently preexisting renal failure exacerbates the metabolic derangements of tumor lysis syndrome. Standard treatment aims to clear high plasma levels of potassium, uric acid, and phosphorus; correct acidosis; and prevent acute renal failure by way of aggressive intravenous hydration; lowering serum potassium levels; use of allopurinol; urinary alkalinization; or renal replacement therapy (if necessary). Allopurinol is the standard of care for treating hyperuricemia of malignancy, but is associated with drawbacks. Recombinant urate oxidase (rasburicase), which recently became available in the United States, provides a safe and effective alternative to allopurinol for lowering uric acid levels and preventing uric acid nephropathy.
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              Febuxostat in the treatment of gout: 5-yr findings of the FOCUS efficacy and safety study.

              This 5-yr study assessed urate-lowering and clinical efficacy and safety of long-term febuxostat therapy in subjects with gout. The primary efficacy end-point was reduction to and maintenance of serum urate (sUA) levels < 6.0 mg/dl. Subjects who completed a previous 28-day study were entered into an open-label extension study and initially received febuxostat 80 mg daily. Between Weeks 4 and 24, dosing could be adjusted to febuxostat 40 or 120 mg. All subjects received gout flare prophylaxis during the first 4 weeks. Gout flares were recorded and treated throughout the study, and sUA, baseline tophi and safety were monitored. Among 116 subjects initially enrolled, dose adjustments were made for 44 (38%) subjects. As a result, 8 subjects received febuxostat 40 mg, 79 received 80 mg, and 29 received 120 mg daily maintenance dose. At 5 yrs, 93% (54/58) of the remaining subjects had sUA < 6.0 mg/dl. Fifty-eight subjects (50%) discontinued prematurely; 38 did so in the first year. Thirteen subjects withdrew due to an adverse event. Sustained reduction of sUA was associated with nearly complete elimination of gout flares. In 26 subjects with a tophus at baseline, resolution was achieved in 69% (18/26) by last visit on study drug at any point during the study (Final Visit). There were no deaths reported during the study. Long-term treatment with febuxostat resulted in durable maintenance of sUA < 6.0 mg/dl for most subjects. There was nearly complete abolition of gout flares in patients completing the study. Baseline tophi resolved in a majority of subjects.
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                Author and article information

                Journal
                Onco Targets Ther
                Onco Targets Ther
                OncoTargets and Therapy
                OncoTargets and therapy
                Dove Medical Press
                1178-6930
                2017
                02 February 2017
                : 10
                : 597-605
                Affiliations
                [1 ]Department of Internal Medicine I, University Hospital Carl Gustav Carus at the Technische Universitaet Dresden, Dresden
                [2 ]German Bone Marrow Donor Center DKMS, Tübigen, Germany
                Author notes
                Correspondence: Nael Alakel, Department of Internal Medicine I, University Hospital Carl Gustav Carus at the Technische Universitaet Dresden, Fetscherstrasse 74, 01307 Dresden, Germany, Tel +49 351 458 2321, Fax +49 351 458 5344, Email nael.alakel@ 123456uniklinikum-dresden.de
                Article
                ott-10-597
                10.2147/OTT.S103864
                5295804
                28203093
                25ad8c23-4ffc-43df-8900-5fe53b4b5d8f
                © 2017 Alakel et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Review

                Oncology & Radiotherapy
                rasburicase,tumor lysis syndrome,hyperuricemia,acute kidney injury
                Oncology & Radiotherapy
                rasburicase, tumor lysis syndrome, hyperuricemia, acute kidney injury

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