Update on Cardiovascular Safety of Tyrosine Kinase Inhibitors: With a Special Focus on QT Interval, Left Ventricular Dysfunction and Overall ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2015-08

AUTHORS

Rashmi R. Shah, Joel Morganroth

ABSTRACT

We previously reviewed the cardiovascular safety of 16 tyrosine kinase inhibitors (TKIs), approved for use in oncology as of 30 September 2012. Since then, the indications for some of them have been widened and an additional nine TKIs have also been approved as of 30 April 2015. Eight of these nine are indicated for use in oncology and one (nintedanib) for idiopathic pulmonary fibrosis. This report is an update on the cardiovascular safety of those 16 TKIs, including the post-marketing data concerning their pro-arrhythmic effects, and reviews the cardiovascular safety of the nine new TKIs approved since (afatinib, cabozantinib, ceritinib, dabrafenib, ibrutinib, lenvatinib, nintedanib, ponatinib, and trametinib). As before, we focus on specific aspects of cardiovascular safety, namely their potential to induce QT interval prolongation, left ventricular (LV) dysfunction and hypertension but now also summarise the risks of arterial thromboembolic events (ATEs) associated with these agents. Of the newer TKIs, cabozantinib and ceritinib have been shown to induce a mild to moderate degree of QTc interval prolongation while cardiac dysfunction has been reported with the use of afatinib, dabrafenib, lenvatinib, ponatinib and trametinib. The label for axitinib was revised to include a new association with cardiac dysfunction. Hypertension is associated with cabozantinib, lenvatinib, nintedanib, ponatinib and trametinib. Ponatinib, within 10 months of its approval in December 2012, required voluntary (temporary) suspension of its marketing until significant safety revisions (restricted indication, additional warnings and precautions about the risk of arterial occlusion and thromboembolic events and amended dose) were made to its label. Compared with the previous 16 TKIs, more of the recently introduced TKIs are associated with the risk of LV dysfunction, and fewer with QT prolongation. Available data on morbidity and mortality associated with TKIs, together with post-marketing experience with lapatinib and ponatinib, emphasise the need for effective pharmacovigilance and ongoing re-assessment of their risk/benefit after approval of these novel agents. If not adequately managed, these cardiovascular effects significantly decrease the quality of life and increase the morbidity and mortality in a population already at high risk. Evidence accumulated over the last decade suggests that their clinical benefit, although worthwhile, is modest and extends only to progression-free survival and complete response without any effect on overall survival. During uncontrolled use in routine clinical practice, their risk/benefit is likely to be inferior to that perceived from highly controlled clinical trials. More... »

PAGES

693-710

References to SciGraph publications

  • 2013-06. Clinical Pharmacology and the Catalysis of Regulatory Science: Opportunities for the Advancement of Drug Development and Evaluation in CLINICAL PHARMACOLOGY & THERAPEUTICS
  • 2013-06. Antipsychotics and Torsadogenic Risk: Signals Emerging from the US FDA Adverse Event Reporting System Database in DRUG SAFETY
  • 2016-01. FGF2 Prevents Sunitinib-Induced Cardiotoxicity in Zebrafish and Cardiomyoblast H9c2 Cells in CARDIOVASCULAR TOXICOLOGY
  • 2015-03. Incidence and relevance of QTc-interval prolongation caused by tyrosine kinase inhibitors in BRITISH JOURNAL OF CANCER
  • 2010-02. Evaluation and Management of Cardiac Safety Using the Electrocardiogram in Oncology Clinical Trials: Focus on Cardiac Repolarization (QTc Interval) in CLINICAL PHARMACOLOGY & THERAPEUTICS
  • 2013-02. Incidence and risk of hypertension with pazopanib in patients with cancer: a meta-analysis in CANCER CHEMOTHERAPY AND PHARMACOLOGY
  • 2013-03. Integrating Clinical Pharmacology Concepts in Individualized Therapy With Tyrosine Kinase Inhibitors in CLINICAL PHARMACOLOGY & THERAPEUTICS
  • 2013-06. Tyrosine Kinase Inhibitors: Their On-Target Toxicities as Potential Indicators of Efficacy in DRUG SAFETY
  • 2015-01. QTc interval prolongation with vascular endothelial growth factor receptor tyrosine kinase inhibitors in BRITISH JOURNAL OF CANCER
  • 2006-02. An Assessment of the Publicly Disseminated Evidence of Safety Used in Decisions to Withdraw Medicinal Products from the UK and US Markets in DRUG SAFETY
  • 2013-02. Chemotherapy plus multitargeted antiangiogenic tyrosine kinase inhibitors or chemotherapy alone in advanced NSCLC: a meta-analysis of randomized controlled trials in EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
  • 2008-10. Medicinal Product Safety on the UK Market — A Ten Year study in DRUG SAFETY
  • 2013-05. Cardiovascular Safety of Tyrosine Kinase Inhibitors: With a Special Focus on Cardiac Repolarisation (QT Interval) in DRUG SAFETY
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s40264-015-0300-1

    DOI

    http://dx.doi.org/10.1007/s40264-015-0300-1

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1025247766

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/26008987


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1102", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Cardiorespiratory Medicine and Haematology", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Medical and Health Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Animals", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Drug-Related Side Effects and Adverse Reactions", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Long QT Syndrome", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Protein Kinase Inhibitors", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Risk Assessment", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Ventricular Dysfunction, Left", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "name": [
                "Rashmi Shah Consultancy Ltd, 8 Birchdale, SL9 7JA, Gerrards Cross, Buckinghamshire, UK"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Shah", 
            "givenName": "Rashmi R.", 
            "id": "sg:person.01223766066.71", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01223766066.71"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "name": [
                "eResearch Technology, Philadelphia, PA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Morganroth", 
            "givenName": "Joel", 
            "id": "sg:person.0756663113.12", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0756663113.12"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "https://doi.org/10.1200/jco.2011.40.3824", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1000021306"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/pds.3395", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001218817"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.critrevonc.2014.12.008", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001644604"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.lungcan.2010.08.012", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001830323"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.critrevonc.2014.04.004", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1002075882"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1200/jco.2011.37.1195", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1003613275"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/1078-0432.ccr-13-0523", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1003733671"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0959-8049(09)70047-4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1004365390"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.2169/internalmedicine.51.6285", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1004751932"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1248/bpb.b12-00778", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005596781"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1111/bcp.12387", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005711132"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0149-2918(98)80007-6", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1006333585"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/cncr.28972", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1007823060"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1200/jco.2010.34.4309", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1012860182"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.ctrv.2014.02.004", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1014404335"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/pds.1742", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1015083994"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/pds.1742", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1015083994"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.ahj.2011.10.018", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1015637041"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s40264-013-0032-z", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016062014", 
              "https://doi.org/10.1007/s40264-013-0032-z"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s40264-013-0032-z", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016062014", 
              "https://doi.org/10.1007/s40264-013-0032-z"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1200/jco.2007.15.6331", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016398351"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/annonc/mdr592", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1020255632"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1371/journal.pone.0055128", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1020989706"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1592/phco.22.8.663.33201", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021238844"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.amjcard.2015.01.016", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021280168"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s40264-013-0050-x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021372637", 
              "https://doi.org/10.1007/s40264-013-0050-x"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/eurjhf/hfq213", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021503685"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1177/0091270006286436", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1022325751"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1111/j.1365-2125.2012.04417.x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1022963821"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.lungcan.2015.01.026", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1023249721"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1586/17512433.2015.974555", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024683180"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00280-012-2025-5", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026870686", 
              "https://doi.org/10.1007/s00280-012-2025-5"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s12012-015-9315-1", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026898938", 
              "https://doi.org/10.1007/s12012-015-9315-1"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/pds.1002", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1029180834"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.rmed.2013.06.005", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1029242263"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/bjc.2014.564", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030201307", 
              "https://doi.org/10.1038/bjc.2014.564"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1200/jco.2009.27.2757", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030212761"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/annonc/mdv063", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030421080"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1200/jco.2011.35.2393", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032014552"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.ctrv.2012.05.001", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032112381"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1111/bcp.12085", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1033840916"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.cardfail.2013.12.018", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1033879942"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1111/bcp.12149", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1034014704"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.ctrv.2014.05.003", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1034663628"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/clpt.2009.214", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1035191393", 
              "https://doi.org/10.1038/clpt.2009.214"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/clpt.2009.214", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1035191393", 
              "https://doi.org/10.1038/clpt.2009.214"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1185/03007995.2014.938730", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1035614566"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.critrevonc.2014.06.003", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1040001435"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/pds.677", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1040997746"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/pds.677", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1040997746"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.taap.2010.08.026", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1041005985"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/bjc.2015.82", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1041526745", 
              "https://doi.org/10.1038/bjc.2015.82"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.2147/ott.s68386", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042611253"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/pds.3333", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042989201"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00228-012-1333-3", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1043176946", 
              "https://doi.org/10.1007/s00228-012-1333-3"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/clpt.2012.247", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1043782698", 
              "https://doi.org/10.1038/clpt.2012.247"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.tcm.2014.07.003", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1044381884"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.2165/00002018-200831100-00012", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1044867085", 
              "https://doi.org/10.2165/00002018-200831100-00012"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1371/journal.pone.0122735", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1044951042"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.leukres.2010.08.020", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1045784442"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s40264-013-0047-5", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1046942550", 
              "https://doi.org/10.1007/s40264-013-0047-5"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/hon.967", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1047272069"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.leukres.2010.01.004", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1048328613"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1046/j.1365-2125.1999.00881.x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1048812036"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1046/j.1365-2125.1999.00881.x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1048812036"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/europace/eut018", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1050069299"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1200/jco.2010.31.9624", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1050117795"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/clpt.2013.32", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1052011427", 
              "https://doi.org/10.1038/clpt.2013.32"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.2165/00002018-200629020-00008", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1052273690", 
              "https://doi.org/10.2165/00002018-200629020-00008"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.2165/00002018-200629020-00008", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1052273690", 
              "https://doi.org/10.2165/00002018-200629020-00008"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/jjco/hyv030", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1059803019"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1200/jco.2003.04.537", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1064203574"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.2174/157488408784293705", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1069214091"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.2741/3377", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1070915563"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.3748/wjg.v21.i8.2573", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1071373433"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.5489/cuaj.2426", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1072920437"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1078190731", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1177/106002808802200117", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1079659497"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1177/106002808802200117", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1079659497"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2015-08", 
        "datePublishedReg": "2015-08-01", 
        "description": "We previously reviewed the cardiovascular safety of 16 tyrosine kinase inhibitors (TKIs), approved for use in oncology as of 30 September 2012. Since then, the indications for some of them have been widened and an additional nine TKIs have also been approved as of 30 April 2015. Eight of these nine are indicated for use in oncology and one (nintedanib) for idiopathic pulmonary fibrosis. This report is an update on the cardiovascular safety of those 16 TKIs, including the post-marketing data concerning their pro-arrhythmic effects, and reviews the cardiovascular safety of the nine new TKIs approved since (afatinib, cabozantinib, ceritinib, dabrafenib, ibrutinib, lenvatinib, nintedanib, ponatinib, and trametinib). As before, we focus on specific aspects of cardiovascular safety, namely their potential to induce QT interval prolongation, left ventricular (LV) dysfunction and hypertension but now also summarise the risks of arterial thromboembolic events (ATEs) associated with these agents. Of the newer TKIs, cabozantinib and ceritinib have been shown to induce a mild to moderate degree of QTc interval prolongation while cardiac dysfunction has been reported with the use of afatinib, dabrafenib, lenvatinib, ponatinib and trametinib. The label for axitinib was revised to include a new association with cardiac dysfunction. Hypertension is associated with cabozantinib, lenvatinib, nintedanib, ponatinib and trametinib. Ponatinib, within 10 months of its approval in December 2012, required voluntary (temporary) suspension of its marketing until significant safety revisions (restricted indication, additional warnings and precautions about the risk of arterial occlusion and thromboembolic events and amended dose) were made to its label. Compared with the previous 16 TKIs, more of the recently introduced TKIs are associated with the risk of LV dysfunction, and fewer with QT prolongation. Available data on morbidity and mortality associated with TKIs, together with post-marketing experience with lapatinib and ponatinib, emphasise the need for effective pharmacovigilance and ongoing re-assessment of their risk/benefit after approval of these novel agents. If not adequately managed, these cardiovascular effects significantly decrease the quality of life and increase the morbidity and mortality in a population already at high risk. Evidence accumulated over the last decade suggests that their clinical benefit, although worthwhile, is modest and extends only to progression-free survival and complete response without any effect on overall survival. During uncontrolled use in routine clinical practice, their risk/benefit is likely to be inferior to that perceived from highly controlled clinical trials.", 
        "genre": "research_article", 
        "id": "sg:pub.10.1007/s40264-015-0300-1", 
        "inLanguage": [
          "en"
        ], 
        "isAccessibleForFree": false, 
        "isPartOf": [
          {
            "id": "sg:journal.1096281", 
            "issn": [
              "0114-5916", 
              "1179-1942"
            ], 
            "name": "Drug Safety", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "8", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "38"
          }
        ], 
        "name": "Update on Cardiovascular Safety of Tyrosine Kinase Inhibitors: With a Special Focus on QT Interval, Left Ventricular Dysfunction and Overall Risk/Benefit", 
        "pagination": "693-710", 
        "productId": [
          {
            "name": "readcube_id", 
            "type": "PropertyValue", 
            "value": [
              "7847c543bea007b38c11ef8ace4621cf8ad21921a4eb1cc8f4bf7c99159e1f2c"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "26008987"
            ]
          }, 
          {
            "name": "nlm_unique_id", 
            "type": "PropertyValue", 
            "value": [
              "9002928"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1007/s40264-015-0300-1"
            ]
          }, 
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1025247766"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1007/s40264-015-0300-1", 
          "https://app.dimensions.ai/details/publication/pub.1025247766"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2019-04-10T20:49", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000001_0000000264/records_8684_00000522.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "http://link.springer.com/10.1007%2Fs40264-015-0300-1"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1007/s40264-015-0300-1'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/s40264-015-0300-1'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s40264-015-0300-1'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s40264-015-0300-1'


     

    This table displays all metadata directly associated to this object as RDF triples.

    333 TRIPLES      21 PREDICATES      108 URIs      28 LITERALS      16 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1007/s40264-015-0300-1 schema:about N3236302eb3db41978ea7749e6ce8faa4
    2 N8b1f447e3baf47a8bec0e9fd320681a2
    3 N9219054350b148e2987a2bb0e05834a6
    4 N929aa0a2d0f84e49b7adbe3b1687b48b
    5 Na1bb050af26e49978f79c00140d979d4
    6 Na1e8e6594aaf49af94bbc5c0bd3deb36
    7 Ne1b4f70d38de4d0bbd454fc7de66cc0a
    8 anzsrc-for:11
    9 anzsrc-for:1102
    10 schema:author Nb093e5a7843143ab9408faaeb57850dd
    11 schema:citation sg:pub.10.1007/s00228-012-1333-3
    12 sg:pub.10.1007/s00280-012-2025-5
    13 sg:pub.10.1007/s12012-015-9315-1
    14 sg:pub.10.1007/s40264-013-0032-z
    15 sg:pub.10.1007/s40264-013-0047-5
    16 sg:pub.10.1007/s40264-013-0050-x
    17 sg:pub.10.1038/bjc.2014.564
    18 sg:pub.10.1038/bjc.2015.82
    19 sg:pub.10.1038/clpt.2009.214
    20 sg:pub.10.1038/clpt.2012.247
    21 sg:pub.10.1038/clpt.2013.32
    22 sg:pub.10.2165/00002018-200629020-00008
    23 sg:pub.10.2165/00002018-200831100-00012
    24 https://app.dimensions.ai/details/publication/pub.1078190731
    25 https://doi.org/10.1002/cncr.28972
    26 https://doi.org/10.1002/hon.967
    27 https://doi.org/10.1002/pds.1002
    28 https://doi.org/10.1002/pds.1742
    29 https://doi.org/10.1002/pds.3333
    30 https://doi.org/10.1002/pds.3395
    31 https://doi.org/10.1002/pds.677
    32 https://doi.org/10.1016/j.ahj.2011.10.018
    33 https://doi.org/10.1016/j.amjcard.2015.01.016
    34 https://doi.org/10.1016/j.cardfail.2013.12.018
    35 https://doi.org/10.1016/j.critrevonc.2014.04.004
    36 https://doi.org/10.1016/j.critrevonc.2014.06.003
    37 https://doi.org/10.1016/j.critrevonc.2014.12.008
    38 https://doi.org/10.1016/j.ctrv.2012.05.001
    39 https://doi.org/10.1016/j.ctrv.2014.02.004
    40 https://doi.org/10.1016/j.ctrv.2014.05.003
    41 https://doi.org/10.1016/j.leukres.2010.01.004
    42 https://doi.org/10.1016/j.leukres.2010.08.020
    43 https://doi.org/10.1016/j.lungcan.2010.08.012
    44 https://doi.org/10.1016/j.lungcan.2015.01.026
    45 https://doi.org/10.1016/j.rmed.2013.06.005
    46 https://doi.org/10.1016/j.taap.2010.08.026
    47 https://doi.org/10.1016/j.tcm.2014.07.003
    48 https://doi.org/10.1016/s0149-2918(98)80007-6
    49 https://doi.org/10.1016/s0959-8049(09)70047-4
    50 https://doi.org/10.1046/j.1365-2125.1999.00881.x
    51 https://doi.org/10.1093/annonc/mdr592
    52 https://doi.org/10.1093/annonc/mdv063
    53 https://doi.org/10.1093/eurjhf/hfq213
    54 https://doi.org/10.1093/europace/eut018
    55 https://doi.org/10.1093/jjco/hyv030
    56 https://doi.org/10.1111/bcp.12085
    57 https://doi.org/10.1111/bcp.12149
    58 https://doi.org/10.1111/bcp.12387
    59 https://doi.org/10.1111/j.1365-2125.2012.04417.x
    60 https://doi.org/10.1158/1078-0432.ccr-13-0523
    61 https://doi.org/10.1177/0091270006286436
    62 https://doi.org/10.1177/106002808802200117
    63 https://doi.org/10.1185/03007995.2014.938730
    64 https://doi.org/10.1200/jco.2003.04.537
    65 https://doi.org/10.1200/jco.2007.15.6331
    66 https://doi.org/10.1200/jco.2009.27.2757
    67 https://doi.org/10.1200/jco.2010.31.9624
    68 https://doi.org/10.1200/jco.2010.34.4309
    69 https://doi.org/10.1200/jco.2011.35.2393
    70 https://doi.org/10.1200/jco.2011.37.1195
    71 https://doi.org/10.1200/jco.2011.40.3824
    72 https://doi.org/10.1248/bpb.b12-00778
    73 https://doi.org/10.1371/journal.pone.0055128
    74 https://doi.org/10.1371/journal.pone.0122735
    75 https://doi.org/10.1586/17512433.2015.974555
    76 https://doi.org/10.1592/phco.22.8.663.33201
    77 https://doi.org/10.2147/ott.s68386
    78 https://doi.org/10.2169/internalmedicine.51.6285
    79 https://doi.org/10.2174/157488408784293705
    80 https://doi.org/10.2741/3377
    81 https://doi.org/10.3748/wjg.v21.i8.2573
    82 https://doi.org/10.5489/cuaj.2426
    83 schema:datePublished 2015-08
    84 schema:datePublishedReg 2015-08-01
    85 schema:description We previously reviewed the cardiovascular safety of 16 tyrosine kinase inhibitors (TKIs), approved for use in oncology as of 30 September 2012. Since then, the indications for some of them have been widened and an additional nine TKIs have also been approved as of 30 April 2015. Eight of these nine are indicated for use in oncology and one (nintedanib) for idiopathic pulmonary fibrosis. This report is an update on the cardiovascular safety of those 16 TKIs, including the post-marketing data concerning their pro-arrhythmic effects, and reviews the cardiovascular safety of the nine new TKIs approved since (afatinib, cabozantinib, ceritinib, dabrafenib, ibrutinib, lenvatinib, nintedanib, ponatinib, and trametinib). As before, we focus on specific aspects of cardiovascular safety, namely their potential to induce QT interval prolongation, left ventricular (LV) dysfunction and hypertension but now also summarise the risks of arterial thromboembolic events (ATEs) associated with these agents. Of the newer TKIs, cabozantinib and ceritinib have been shown to induce a mild to moderate degree of QTc interval prolongation while cardiac dysfunction has been reported with the use of afatinib, dabrafenib, lenvatinib, ponatinib and trametinib. The label for axitinib was revised to include a new association with cardiac dysfunction. Hypertension is associated with cabozantinib, lenvatinib, nintedanib, ponatinib and trametinib. Ponatinib, within 10 months of its approval in December 2012, required voluntary (temporary) suspension of its marketing until significant safety revisions (restricted indication, additional warnings and precautions about the risk of arterial occlusion and thromboembolic events and amended dose) were made to its label. Compared with the previous 16 TKIs, more of the recently introduced TKIs are associated with the risk of LV dysfunction, and fewer with QT prolongation. Available data on morbidity and mortality associated with TKIs, together with post-marketing experience with lapatinib and ponatinib, emphasise the need for effective pharmacovigilance and ongoing re-assessment of their risk/benefit after approval of these novel agents. If not adequately managed, these cardiovascular effects significantly decrease the quality of life and increase the morbidity and mortality in a population already at high risk. Evidence accumulated over the last decade suggests that their clinical benefit, although worthwhile, is modest and extends only to progression-free survival and complete response without any effect on overall survival. During uncontrolled use in routine clinical practice, their risk/benefit is likely to be inferior to that perceived from highly controlled clinical trials.
    86 schema:genre research_article
    87 schema:inLanguage en
    88 schema:isAccessibleForFree false
    89 schema:isPartOf N5dd5caaa39314ef2b319cf6764945149
    90 Nc4c647e4bdde474d9ac6d54181818cb0
    91 sg:journal.1096281
    92 schema:name Update on Cardiovascular Safety of Tyrosine Kinase Inhibitors: With a Special Focus on QT Interval, Left Ventricular Dysfunction and Overall Risk/Benefit
    93 schema:pagination 693-710
    94 schema:productId N71e1bbeddeb543d9805154232357936d
    95 Nae685a5f208f4590b6a70f79378a6836
    96 Nd29075f0b7974b908c52d1515d3d27cd
    97 Nd333d9e40cab4922af162c2ac8e659cc
    98 Ne15249aade6940bf90c014ccc8c1e228
    99 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025247766
    100 https://doi.org/10.1007/s40264-015-0300-1
    101 schema:sdDatePublished 2019-04-10T20:49
    102 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    103 schema:sdPublisher Nddab77c3bdac4adba107b34669d05744
    104 schema:url http://link.springer.com/10.1007%2Fs40264-015-0300-1
    105 sgo:license sg:explorer/license/
    106 sgo:sdDataset articles
    107 rdf:type schema:ScholarlyArticle
    108 N01288b47eb4b400eb3139f2a8da8781c rdf:first sg:person.0756663113.12
    109 rdf:rest rdf:nil
    110 N3236302eb3db41978ea7749e6ce8faa4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    111 schema:name Risk Assessment
    112 rdf:type schema:DefinedTerm
    113 N5dc23aaac404410b87c70449faf26834 schema:name eResearch Technology, Philadelphia, PA, USA
    114 rdf:type schema:Organization
    115 N5dd5caaa39314ef2b319cf6764945149 schema:volumeNumber 38
    116 rdf:type schema:PublicationVolume
    117 N71e1bbeddeb543d9805154232357936d schema:name doi
    118 schema:value 10.1007/s40264-015-0300-1
    119 rdf:type schema:PropertyValue
    120 N8b1f447e3baf47a8bec0e9fd320681a2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    121 schema:name Long QT Syndrome
    122 rdf:type schema:DefinedTerm
    123 N9219054350b148e2987a2bb0e05834a6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    124 schema:name Protein Kinase Inhibitors
    125 rdf:type schema:DefinedTerm
    126 N929aa0a2d0f84e49b7adbe3b1687b48b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    127 schema:name Animals
    128 rdf:type schema:DefinedTerm
    129 Na1bb050af26e49978f79c00140d979d4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    130 schema:name Ventricular Dysfunction, Left
    131 rdf:type schema:DefinedTerm
    132 Na1e8e6594aaf49af94bbc5c0bd3deb36 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    133 schema:name Humans
    134 rdf:type schema:DefinedTerm
    135 Nae685a5f208f4590b6a70f79378a6836 schema:name dimensions_id
    136 schema:value pub.1025247766
    137 rdf:type schema:PropertyValue
    138 Nb093e5a7843143ab9408faaeb57850dd rdf:first sg:person.01223766066.71
    139 rdf:rest N01288b47eb4b400eb3139f2a8da8781c
    140 Nc4c647e4bdde474d9ac6d54181818cb0 schema:issueNumber 8
    141 rdf:type schema:PublicationIssue
    142 Nd29075f0b7974b908c52d1515d3d27cd schema:name pubmed_id
    143 schema:value 26008987
    144 rdf:type schema:PropertyValue
    145 Nd333d9e40cab4922af162c2ac8e659cc schema:name nlm_unique_id
    146 schema:value 9002928
    147 rdf:type schema:PropertyValue
    148 Nddab77c3bdac4adba107b34669d05744 schema:name Springer Nature - SN SciGraph project
    149 rdf:type schema:Organization
    150 Ne15249aade6940bf90c014ccc8c1e228 schema:name readcube_id
    151 schema:value 7847c543bea007b38c11ef8ace4621cf8ad21921a4eb1cc8f4bf7c99159e1f2c
    152 rdf:type schema:PropertyValue
    153 Ne1b4f70d38de4d0bbd454fc7de66cc0a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    154 schema:name Drug-Related Side Effects and Adverse Reactions
    155 rdf:type schema:DefinedTerm
    156 Nf007ac3779e348ee87820272feb57f69 schema:name Rashmi Shah Consultancy Ltd, 8 Birchdale, SL9 7JA, Gerrards Cross, Buckinghamshire, UK
    157 rdf:type schema:Organization
    158 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    159 schema:name Medical and Health Sciences
    160 rdf:type schema:DefinedTerm
    161 anzsrc-for:1102 schema:inDefinedTermSet anzsrc-for:
    162 schema:name Cardiorespiratory Medicine and Haematology
    163 rdf:type schema:DefinedTerm
    164 sg:journal.1096281 schema:issn 0114-5916
    165 1179-1942
    166 schema:name Drug Safety
    167 rdf:type schema:Periodical
    168 sg:person.01223766066.71 schema:affiliation Nf007ac3779e348ee87820272feb57f69
    169 schema:familyName Shah
    170 schema:givenName Rashmi R.
    171 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01223766066.71
    172 rdf:type schema:Person
    173 sg:person.0756663113.12 schema:affiliation N5dc23aaac404410b87c70449faf26834
    174 schema:familyName Morganroth
    175 schema:givenName Joel
    176 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0756663113.12
    177 rdf:type schema:Person
    178 sg:pub.10.1007/s00228-012-1333-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043176946
    179 https://doi.org/10.1007/s00228-012-1333-3
    180 rdf:type schema:CreativeWork
    181 sg:pub.10.1007/s00280-012-2025-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026870686
    182 https://doi.org/10.1007/s00280-012-2025-5
    183 rdf:type schema:CreativeWork
    184 sg:pub.10.1007/s12012-015-9315-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026898938
    185 https://doi.org/10.1007/s12012-015-9315-1
    186 rdf:type schema:CreativeWork
    187 sg:pub.10.1007/s40264-013-0032-z schema:sameAs https://app.dimensions.ai/details/publication/pub.1016062014
    188 https://doi.org/10.1007/s40264-013-0032-z
    189 rdf:type schema:CreativeWork
    190 sg:pub.10.1007/s40264-013-0047-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046942550
    191 https://doi.org/10.1007/s40264-013-0047-5
    192 rdf:type schema:CreativeWork
    193 sg:pub.10.1007/s40264-013-0050-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1021372637
    194 https://doi.org/10.1007/s40264-013-0050-x
    195 rdf:type schema:CreativeWork
    196 sg:pub.10.1038/bjc.2014.564 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030201307
    197 https://doi.org/10.1038/bjc.2014.564
    198 rdf:type schema:CreativeWork
    199 sg:pub.10.1038/bjc.2015.82 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041526745
    200 https://doi.org/10.1038/bjc.2015.82
    201 rdf:type schema:CreativeWork
    202 sg:pub.10.1038/clpt.2009.214 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035191393
    203 https://doi.org/10.1038/clpt.2009.214
    204 rdf:type schema:CreativeWork
    205 sg:pub.10.1038/clpt.2012.247 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043782698
    206 https://doi.org/10.1038/clpt.2012.247
    207 rdf:type schema:CreativeWork
    208 sg:pub.10.1038/clpt.2013.32 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052011427
    209 https://doi.org/10.1038/clpt.2013.32
    210 rdf:type schema:CreativeWork
    211 sg:pub.10.2165/00002018-200629020-00008 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052273690
    212 https://doi.org/10.2165/00002018-200629020-00008
    213 rdf:type schema:CreativeWork
    214 sg:pub.10.2165/00002018-200831100-00012 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044867085
    215 https://doi.org/10.2165/00002018-200831100-00012
    216 rdf:type schema:CreativeWork
    217 https://app.dimensions.ai/details/publication/pub.1078190731 schema:CreativeWork
    218 https://doi.org/10.1002/cncr.28972 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007823060
    219 rdf:type schema:CreativeWork
    220 https://doi.org/10.1002/hon.967 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047272069
    221 rdf:type schema:CreativeWork
    222 https://doi.org/10.1002/pds.1002 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029180834
    223 rdf:type schema:CreativeWork
    224 https://doi.org/10.1002/pds.1742 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015083994
    225 rdf:type schema:CreativeWork
    226 https://doi.org/10.1002/pds.3333 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042989201
    227 rdf:type schema:CreativeWork
    228 https://doi.org/10.1002/pds.3395 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001218817
    229 rdf:type schema:CreativeWork
    230 https://doi.org/10.1002/pds.677 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040997746
    231 rdf:type schema:CreativeWork
    232 https://doi.org/10.1016/j.ahj.2011.10.018 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015637041
    233 rdf:type schema:CreativeWork
    234 https://doi.org/10.1016/j.amjcard.2015.01.016 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021280168
    235 rdf:type schema:CreativeWork
    236 https://doi.org/10.1016/j.cardfail.2013.12.018 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033879942
    237 rdf:type schema:CreativeWork
    238 https://doi.org/10.1016/j.critrevonc.2014.04.004 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002075882
    239 rdf:type schema:CreativeWork
    240 https://doi.org/10.1016/j.critrevonc.2014.06.003 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040001435
    241 rdf:type schema:CreativeWork
    242 https://doi.org/10.1016/j.critrevonc.2014.12.008 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001644604
    243 rdf:type schema:CreativeWork
    244 https://doi.org/10.1016/j.ctrv.2012.05.001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032112381
    245 rdf:type schema:CreativeWork
    246 https://doi.org/10.1016/j.ctrv.2014.02.004 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014404335
    247 rdf:type schema:CreativeWork
    248 https://doi.org/10.1016/j.ctrv.2014.05.003 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034663628
    249 rdf:type schema:CreativeWork
    250 https://doi.org/10.1016/j.leukres.2010.01.004 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048328613
    251 rdf:type schema:CreativeWork
    252 https://doi.org/10.1016/j.leukres.2010.08.020 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045784442
    253 rdf:type schema:CreativeWork
    254 https://doi.org/10.1016/j.lungcan.2010.08.012 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001830323
    255 rdf:type schema:CreativeWork
    256 https://doi.org/10.1016/j.lungcan.2015.01.026 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023249721
    257 rdf:type schema:CreativeWork
    258 https://doi.org/10.1016/j.rmed.2013.06.005 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029242263
    259 rdf:type schema:CreativeWork
    260 https://doi.org/10.1016/j.taap.2010.08.026 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041005985
    261 rdf:type schema:CreativeWork
    262 https://doi.org/10.1016/j.tcm.2014.07.003 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044381884
    263 rdf:type schema:CreativeWork
    264 https://doi.org/10.1016/s0149-2918(98)80007-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006333585
    265 rdf:type schema:CreativeWork
    266 https://doi.org/10.1016/s0959-8049(09)70047-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004365390
    267 rdf:type schema:CreativeWork
    268 https://doi.org/10.1046/j.1365-2125.1999.00881.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1048812036
    269 rdf:type schema:CreativeWork
    270 https://doi.org/10.1093/annonc/mdr592 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020255632
    271 rdf:type schema:CreativeWork
    272 https://doi.org/10.1093/annonc/mdv063 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030421080
    273 rdf:type schema:CreativeWork
    274 https://doi.org/10.1093/eurjhf/hfq213 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021503685
    275 rdf:type schema:CreativeWork
    276 https://doi.org/10.1093/europace/eut018 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050069299
    277 rdf:type schema:CreativeWork
    278 https://doi.org/10.1093/jjco/hyv030 schema:sameAs https://app.dimensions.ai/details/publication/pub.1059803019
    279 rdf:type schema:CreativeWork
    280 https://doi.org/10.1111/bcp.12085 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033840916
    281 rdf:type schema:CreativeWork
    282 https://doi.org/10.1111/bcp.12149 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034014704
    283 rdf:type schema:CreativeWork
    284 https://doi.org/10.1111/bcp.12387 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005711132
    285 rdf:type schema:CreativeWork
    286 https://doi.org/10.1111/j.1365-2125.2012.04417.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1022963821
    287 rdf:type schema:CreativeWork
    288 https://doi.org/10.1158/1078-0432.ccr-13-0523 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003733671
    289 rdf:type schema:CreativeWork
    290 https://doi.org/10.1177/0091270006286436 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022325751
    291 rdf:type schema:CreativeWork
    292 https://doi.org/10.1177/106002808802200117 schema:sameAs https://app.dimensions.ai/details/publication/pub.1079659497
    293 rdf:type schema:CreativeWork
    294 https://doi.org/10.1185/03007995.2014.938730 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035614566
    295 rdf:type schema:CreativeWork
    296 https://doi.org/10.1200/jco.2003.04.537 schema:sameAs https://app.dimensions.ai/details/publication/pub.1064203574
    297 rdf:type schema:CreativeWork
    298 https://doi.org/10.1200/jco.2007.15.6331 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016398351
    299 rdf:type schema:CreativeWork
    300 https://doi.org/10.1200/jco.2009.27.2757 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030212761
    301 rdf:type schema:CreativeWork
    302 https://doi.org/10.1200/jco.2010.31.9624 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050117795
    303 rdf:type schema:CreativeWork
    304 https://doi.org/10.1200/jco.2010.34.4309 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012860182
    305 rdf:type schema:CreativeWork
    306 https://doi.org/10.1200/jco.2011.35.2393 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032014552
    307 rdf:type schema:CreativeWork
    308 https://doi.org/10.1200/jco.2011.37.1195 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003613275
    309 rdf:type schema:CreativeWork
    310 https://doi.org/10.1200/jco.2011.40.3824 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000021306
    311 rdf:type schema:CreativeWork
    312 https://doi.org/10.1248/bpb.b12-00778 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005596781
    313 rdf:type schema:CreativeWork
    314 https://doi.org/10.1371/journal.pone.0055128 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020989706
    315 rdf:type schema:CreativeWork
    316 https://doi.org/10.1371/journal.pone.0122735 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044951042
    317 rdf:type schema:CreativeWork
    318 https://doi.org/10.1586/17512433.2015.974555 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024683180
    319 rdf:type schema:CreativeWork
    320 https://doi.org/10.1592/phco.22.8.663.33201 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021238844
    321 rdf:type schema:CreativeWork
    322 https://doi.org/10.2147/ott.s68386 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042611253
    323 rdf:type schema:CreativeWork
    324 https://doi.org/10.2169/internalmedicine.51.6285 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004751932
    325 rdf:type schema:CreativeWork
    326 https://doi.org/10.2174/157488408784293705 schema:sameAs https://app.dimensions.ai/details/publication/pub.1069214091
    327 rdf:type schema:CreativeWork
    328 https://doi.org/10.2741/3377 schema:sameAs https://app.dimensions.ai/details/publication/pub.1070915563
    329 rdf:type schema:CreativeWork
    330 https://doi.org/10.3748/wjg.v21.i8.2573 schema:sameAs https://app.dimensions.ai/details/publication/pub.1071373433
    331 rdf:type schema:CreativeWork
    332 https://doi.org/10.5489/cuaj.2426 schema:sameAs https://app.dimensions.ai/details/publication/pub.1072920437
    333 rdf:type schema:CreativeWork
     




    Preview window. Press ESC to close (or click here)


    ...