View in EDS

Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib.

Saved in:
Bibliographic Details
Title: Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib.
Authors: Chu TF (AUTHOR), Rupnick MA (AUTHOR), Kerkela R (AUTHOR), Dallabrida SM (AUTHOR), Zurakowski D (AUTHOR), Nguyen L (AUTHOR), Woulfe K (AUTHOR), Pravda E (AUTHOR), Cassiola F (AUTHOR), Desai J (AUTHOR), George S (AUTHOR), Morgan JA (AUTHOR), Harris DM (AUTHOR), Ismail NS (AUTHOR), Chen JH (AUTHOR), Schoen FJ (AUTHOR), Van den Abbeele AD (AUTHOR), Demetri GD (AUTHOR), Force T (AUTHOR), Chen MH (AUTHOR)
Source: Lancet. 12/15/2007, Vol. 370 Issue 9604, p2011-2019. 9p.
Abstract: Background: Sunitinib, a multitargeted tyrosine-kinase inhibitor, which is approved by both US and European Commission regulatory agencies for clinical use, extends survival of patients with metastatic renal-cell carcinoma and gastrointestinal stromal tumours, but concerns have arisen about its cardiac safety. We therefore assessed the cardiovascular risk associated with sunitinib in patients with metastatic gastrointestinal stromal tumours.Methods: We retrospectively reviewed all cardiovascular events in 75 patients with imatinib-resistant, metastatic, gastrointestinal stromal tumours who had been enrolled in a phase I/II trial investigating the efficacy of sunitinib. The composite cardiovascular endpoint was cardiac death, myocardial infarction, and congestive heart failure. We also examined sunitinib's effects on left ventricular ejection fraction (LVEF) and blood pressure. We investigated potential mechanisms of sunitinib-associated cardiac effects by studies in isolated rat cardiomyocytes and in mice.Findings: Eight of 75 (11%) patients given repeating cycles of sunitinib in the phase I/II trial had a cardiovascular event, with congestive heart failure recorded in six of 75 (8%). Ten of 36 (28%) patients treated at the approved sunitinib dose had absolute LVEF reductions in ejection fraction (EF) of at least 10%, and seven of 36 (19%) had LVEF reductions of 15 EF% or more. Sunitinib induced increases in mean systolic and diastolic blood pressure, and 35 of 75 (47%) individuals developed hypertension (>150/100 mm Hg). Congestive heart failure and left ventricular dysfunction generally responded to sunitinib being withheld and institution of medical management. Sunitinib caused mitochondrial injury and cardiomyocyte apoptosis in mice and in cultured rat cardiomyocytes.Interpretation: Left ventricular dysfunction might be due, in part, to direct cardiomyocyte toxicity, exacerbated by hypertension. Patients treated with sunitinib should be closely monitored for hypertension and LVEF reduction, especially those with a history of coronary artery disease or cardiac risk factors. [ABSTRACT FROM AUTHOR]
Copyright of Lancet is the property of Lancet and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
FullText Text:
  Availability: 0
Header DbId: pbh
DbLabel: Psychology and Behavioral Sciences Collection
An: 105835237
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Chu+TF%22">Chu TF</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Rupnick+MA%22">Rupnick MA</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kerkela+R%22">Kerkela R</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Dallabrida+SM%22">Dallabrida SM</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zurakowski+D%22">Zurakowski D</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Nguyen+L%22">Nguyen L</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Woulfe+K%22">Woulfe K</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Pravda+E%22">Pravda E</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Cassiola+F%22">Cassiola F</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Desai+J%22">Desai J</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22George+S%22">George S</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Morgan+JA%22">Morgan JA</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Harris+DM%22">Harris DM</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ismail+NS%22">Ismail NS</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chen+JH%22">Chen JH</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Schoen+FJ%22">Schoen FJ</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Van+den+Abbeele+AD%22">Van den Abbeele AD</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Demetri+GD%22">Demetri GD</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Force+T%22">Force T</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chen+MH%22">Chen MH</searchLink> (AUTHOR)
– Name: TitleSource
  Label: Source
  Group: Src
  Data: <searchLink fieldCode="JN" term="%22Lancet%22">Lancet</searchLink>. 12/15/2007, Vol. 370 Issue 9604, p2011-2019. 9p.
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: <bold>Background: </bold>Sunitinib, a multitargeted tyrosine-kinase inhibitor, which is approved by both US and European Commission regulatory agencies for clinical use, extends survival of patients with metastatic renal-cell carcinoma and gastrointestinal stromal tumours, but concerns have arisen about its cardiac safety. We therefore assessed the cardiovascular risk associated with sunitinib in patients with metastatic gastrointestinal stromal tumours.<bold>Methods: </bold>We retrospectively reviewed all cardiovascular events in 75 patients with imatinib-resistant, metastatic, gastrointestinal stromal tumours who had been enrolled in a phase I/II trial investigating the efficacy of sunitinib. The composite cardiovascular endpoint was cardiac death, myocardial infarction, and congestive heart failure. We also examined sunitinib's effects on left ventricular ejection fraction (LVEF) and blood pressure. We investigated potential mechanisms of sunitinib-associated cardiac effects by studies in isolated rat cardiomyocytes and in mice.<bold>Findings: </bold>Eight of 75 (11%) patients given repeating cycles of sunitinib in the phase I/II trial had a cardiovascular event, with congestive heart failure recorded in six of 75 (8%). Ten of 36 (28%) patients treated at the approved sunitinib dose had absolute LVEF reductions in ejection fraction (EF) of at least 10%, and seven of 36 (19%) had LVEF reductions of 15 EF% or more. Sunitinib induced increases in mean systolic and diastolic blood pressure, and 35 of 75 (47%) individuals developed hypertension (>150/100 mm Hg). Congestive heart failure and left ventricular dysfunction generally responded to sunitinib being withheld and institution of medical management. Sunitinib caused mitochondrial injury and cardiomyocyte apoptosis in mice and in cultured rat cardiomyocytes.<bold>Interpretation: </bold>Left ventricular dysfunction might be due, in part, to direct cardiomyocyte toxicity, exacerbated by hypertension. Patients treated with sunitinib should be closely monitored for hypertension and LVEF reduction, especially those with a history of coronary artery disease or cardiac risk factors. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Lancet is the property of Lancet and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=105835237
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1016/s0140-6736(07)61865-0
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 9
        StartPage: 2011
    Titles:
      – TitleFull: Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Chu TF
      – PersonEntity:
          Name:
            NameFull: Rupnick MA
      – PersonEntity:
          Name:
            NameFull: Kerkela R
      – PersonEntity:
          Name:
            NameFull: Dallabrida SM
      – PersonEntity:
          Name:
            NameFull: Zurakowski D
      – PersonEntity:
          Name:
            NameFull: Nguyen L
      – PersonEntity:
          Name:
            NameFull: Woulfe K
      – PersonEntity:
          Name:
            NameFull: Pravda E
      – PersonEntity:
          Name:
            NameFull: Cassiola F
      – PersonEntity:
          Name:
            NameFull: Desai J
      – PersonEntity:
          Name:
            NameFull: George S
      – PersonEntity:
          Name:
            NameFull: Morgan JA
      – PersonEntity:
          Name:
            NameFull: Harris DM
      – PersonEntity:
          Name:
            NameFull: Ismail NS
      – PersonEntity:
          Name:
            NameFull: Chen JH
      – PersonEntity:
          Name:
            NameFull: Schoen FJ
      – PersonEntity:
          Name:
            NameFull: Van den Abbeele AD
      – PersonEntity:
          Name:
            NameFull: Demetri GD
      – PersonEntity:
          Name:
            NameFull: Force T
      – PersonEntity:
          Name:
            NameFull: Chen MH
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 15
              M: 12
              Text: 12/15/2007
              Type: published
              Y: 2007
          Identifiers:
            – Type: issn-print
              Value: 01406736
          Numbering:
            – Type: volume
              Value: 370
            – Type: issue
              Value: 9604
          Titles:
            – TitleFull: Lancet
              Type: main
ResultId 1