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Optimizing management of ruxolitinib in patients with myelofibrosis: the need for individualized dosing
Ruxolitinib, an oral JAK1 and JAK2 inhibitor, is approved in the US for patients with intermediate or high-risk myelofibrosis (MF), a chronic neoplasm associated with aberrant myeloproliferation, progressive bone marrow fibrosis, splenomegaly, and burdensome symptoms. Phase III clinical studies have...
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Published in: | Journal of hematology and oncology 2013-10, Vol.6 (1), p.79-79, Article 79 |
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description | Ruxolitinib, an oral JAK1 and JAK2 inhibitor, is approved in the US for patients with intermediate or high-risk myelofibrosis (MF), a chronic neoplasm associated with aberrant myeloproliferation, progressive bone marrow fibrosis, splenomegaly, and burdensome symptoms. Phase III clinical studies have shown that ruxolitinib reduces splenomegaly and alleviates MF-related symptoms, with concomitant improvements in quality of life measures, for the overwhelming majority of treated patients. In addition, ruxolitinib provided an overall survival advantage as compared with either placebo or what was previously considered best available therapy in the two phase III studies. The most common adverse events with ruxolitinib treatment include dose-dependent anemia and thrombocytopenia, which are expected based on its mechanism of action. Experience from the phase III studies shows that these hematologic events can be managed effectively with dose modifications, temporary treatment interruptions, as well as red blood cell transfusions in the case of anemia and, importantly, are rarely cause for permanent treatment discontinuation. This review summarizes data supporting appropriate individualized patient management through careful monitoring of blood counts and dose titration as needed in order to maximize treatment benefit. |
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Phase III clinical studies have shown that ruxolitinib reduces splenomegaly and alleviates MF-related symptoms, with concomitant improvements in quality of life measures, for the overwhelming majority of treated patients. In addition, ruxolitinib provided an overall survival advantage as compared with either placebo or what was previously considered best available therapy in the two phase III studies. The most common adverse events with ruxolitinib treatment include dose-dependent anemia and thrombocytopenia, which are expected based on its mechanism of action. Experience from the phase III studies shows that these hematologic events can be managed effectively with dose modifications, temporary treatment interruptions, as well as red blood cell transfusions in the case of anemia and, importantly, are rarely cause for permanent treatment discontinuation. 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This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.</rights><rights>Copyright © 2013 Mesa and Cortes; licensee BioMed Central Ltd. 2013 Mesa and Cortes; licensee BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b574t-6fc626b777f482519cb0e84f22f9f1756fec00ff814e33c29dd2313d8793cae83</citedby><cites>FETCH-LOGICAL-b574t-6fc626b777f482519cb0e84f22f9f1756fec00ff814e33c29dd2313d8793cae83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222119/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1446722049?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,25731,27901,27902,36989,44566,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24283870$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mesa, Ruben A</creatorcontrib><creatorcontrib>Cortes, Jorge</creatorcontrib><title>Optimizing management of ruxolitinib in patients with myelofibrosis: the need for individualized dosing</title><title>Journal of hematology and oncology</title><addtitle>J Hematol Oncol</addtitle><description>Ruxolitinib, an oral JAK1 and JAK2 inhibitor, is approved in the US for patients with intermediate or high-risk myelofibrosis (MF), a chronic neoplasm associated with aberrant myeloproliferation, progressive bone marrow fibrosis, splenomegaly, and burdensome symptoms. Phase III clinical studies have shown that ruxolitinib reduces splenomegaly and alleviates MF-related symptoms, with concomitant improvements in quality of life measures, for the overwhelming majority of treated patients. In addition, ruxolitinib provided an overall survival advantage as compared with either placebo or what was previously considered best available therapy in the two phase III studies. The most common adverse events with ruxolitinib treatment include dose-dependent anemia and thrombocytopenia, which are expected based on its mechanism of action. Experience from the phase III studies shows that these hematologic events can be managed effectively with dose modifications, temporary treatment interruptions, as well as red blood cell transfusions in the case of anemia and, importantly, are rarely cause for permanent treatment discontinuation. This review summarizes data supporting appropriate individualized patient management through careful monitoring of blood counts and dose titration as needed in order to maximize treatment benefit.</description><subject>Abdomen</subject><subject>Anemia</subject><subject>Anemia - chemically induced</subject><subject>Anemia - drug therapy</subject><subject>Blood</subject><subject>Blood platelets</subject><subject>Cancer</subject><subject>Colleges & universities</subject><subject>Comparative analysis</subject><subject>Complications and side effects</subject><subject>Drug dosages</subject><subject>Drug therapy</subject><subject>Genetic aspects</subject><subject>Hematology</subject><subject>Humans</subject><subject>Leukemia</subject><subject>Medical research</subject><subject>Medical treatment</subject><subject>Medicine, Experimental</subject><subject>Myelofibrosis</subject><subject>Nitriles</subject><subject>Oncology</subject><subject>Pain</subject><subject>Patients</subject><subject>Precision Medicine</subject><subject>Primary Myelofibrosis - drug therapy</subject><subject>Primary Myelofibrosis - pathology</subject><subject>Pyrazoles - administration & dosage</subject><subject>Pyrazoles - adverse effects</subject><subject>Pyrimidines</subject><subject>Review</subject><subject>Spleen</subject><subject>Thrombocytopenia - chemically induced</subject><subject>Thrombocytopenia - drug therapy</subject><issn>1756-8722</issn><issn>1756-8722</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><recordid>eNp1kk1r3DAQhk1padK01x6LoNCbU32tZPdQWEK_IJBLexayLNkTbGkryWmTX1-ZpMsuTdFBYuadh3lHU1WvCT4npBHvidyIupGU1qKW7ZPqdB94evA-qV6kdI2xIC3Fz6sTymnDGolPq-Fql2GGO_ADmrXXg52tzyg4FJffYYIMHjoEHu10hpJJ6BfkEc23dgoOuhgSpA8ojxZ5a3vkQiziHm6gX_QEdyXUF4kfXlbPnJ6SffVwn1U_Pn_6fvG1vrz68u1ie1l3G8lzLZwRVHRSSscbuiGt6bBtuKPUtW6146zB2LmGcMuYoW3fU0ZY38iWGW0bdlZ9vOfulm62vSktRz2pXYRZx1sVNKjjjIdRDeFGcUopIW0BbO8BHYT_AI4zJsxq7Uytg1ZCyZXx9qGJGH4uNmV1HZboi29FOBdFh_mBatCTVeBdKDwzQzJqu2FcipYSWlTnj6jK6e0MJnjroMSPCt4dFIxWT3lMYVoyBJ8eJZvyiylatzdJsFqX619bbw5nu5f_3Sb2B8elyyU</recordid><startdate>20131022</startdate><enddate>20131022</enddate><creator>Mesa, Ruben A</creator><creator>Cortes, Jorge</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>20131022</creationdate><title>Optimizing management of ruxolitinib in patients with myelofibrosis: the need for individualized dosing</title><author>Mesa, Ruben A ; Cortes, Jorge</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b574t-6fc626b777f482519cb0e84f22f9f1756fec00ff814e33c29dd2313d8793cae83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Abdomen</topic><topic>Anemia</topic><topic>Anemia - chemically induced</topic><topic>Anemia - drug therapy</topic><topic>Blood</topic><topic>Blood platelets</topic><topic>Cancer</topic><topic>Colleges & universities</topic><topic>Comparative analysis</topic><topic>Complications and side effects</topic><topic>Drug dosages</topic><topic>Drug therapy</topic><topic>Genetic aspects</topic><topic>Hematology</topic><topic>Humans</topic><topic>Leukemia</topic><topic>Medical research</topic><topic>Medical treatment</topic><topic>Medicine, Experimental</topic><topic>Myelofibrosis</topic><topic>Nitriles</topic><topic>Oncology</topic><topic>Pain</topic><topic>Patients</topic><topic>Precision Medicine</topic><topic>Primary Myelofibrosis - drug therapy</topic><topic>Primary Myelofibrosis - pathology</topic><topic>Pyrazoles - administration & dosage</topic><topic>Pyrazoles - adverse effects</topic><topic>Pyrimidines</topic><topic>Review</topic><topic>Spleen</topic><topic>Thrombocytopenia - chemically induced</topic><topic>Thrombocytopenia - drug therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mesa, Ruben A</creatorcontrib><creatorcontrib>Cortes, Jorge</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of hematology and oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mesa, Ruben A</au><au>Cortes, Jorge</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Optimizing management of ruxolitinib in patients with myelofibrosis: the need for individualized dosing</atitle><jtitle>Journal of hematology and oncology</jtitle><addtitle>J Hematol Oncol</addtitle><date>2013-10-22</date><risdate>2013</risdate><volume>6</volume><issue>1</issue><spage>79</spage><epage>79</epage><pages>79-79</pages><artnum>79</artnum><issn>1756-8722</issn><eissn>1756-8722</eissn><abstract>Ruxolitinib, an oral JAK1 and JAK2 inhibitor, is approved in the US for patients with intermediate or high-risk myelofibrosis (MF), a chronic neoplasm associated with aberrant myeloproliferation, progressive bone marrow fibrosis, splenomegaly, and burdensome symptoms. Phase III clinical studies have shown that ruxolitinib reduces splenomegaly and alleviates MF-related symptoms, with concomitant improvements in quality of life measures, for the overwhelming majority of treated patients. In addition, ruxolitinib provided an overall survival advantage as compared with either placebo or what was previously considered best available therapy in the two phase III studies. The most common adverse events with ruxolitinib treatment include dose-dependent anemia and thrombocytopenia, which are expected based on its mechanism of action. Experience from the phase III studies shows that these hematologic events can be managed effectively with dose modifications, temporary treatment interruptions, as well as red blood cell transfusions in the case of anemia and, importantly, are rarely cause for permanent treatment discontinuation. 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subjects | Abdomen Anemia Anemia - chemically induced Anemia - drug therapy Blood Blood platelets Cancer Colleges & universities Comparative analysis Complications and side effects Drug dosages Drug therapy Genetic aspects Hematology Humans Leukemia Medical research Medical treatment Medicine, Experimental Myelofibrosis Nitriles Oncology Pain Patients Precision Medicine Primary Myelofibrosis - drug therapy Primary Myelofibrosis - pathology Pyrazoles - administration & dosage Pyrazoles - adverse effects Pyrimidines Review Spleen Thrombocytopenia - chemically induced Thrombocytopenia - drug therapy |
title | Optimizing management of ruxolitinib in patients with myelofibrosis: the need for individualized dosing |
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