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Precise safety pharmacology studies of lapatinib for onco-cardiology assessed using in vivo canine models
Cancer chemotherapies have improved prognosis in cancer patients, resulting in a large and rapidly increasing number of cancer survivors. “Onco-cardiology” or “cardio-oncology” is a new discipline for addressing the unanticipated cardiac side effects of newly developed cancer drugs. Lapatinib, a tyr...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971088/ https://www.ncbi.nlm.nih.gov/pubmed/31959820 http://dx.doi.org/10.1038/s41598-020-57601-x |
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author | Ando, Kentaro Wada, Takeshi Cao, Xin |
author_facet | Ando, Kentaro Wada, Takeshi Cao, Xin |
author_sort | Ando, Kentaro |
collection | PubMed |
description | Cancer chemotherapies have improved prognosis in cancer patients, resulting in a large and rapidly increasing number of cancer survivors. “Onco-cardiology” or “cardio-oncology” is a new discipline for addressing the unanticipated cardiac side effects of newly developed cancer drugs. Lapatinib, a tyrosine kinase inhibitor suppressing the epidermal growth factor receptor and ErbB2, has been used in advanced or metastatic breast cancer treatment. Reportedly, lapatinib has induced cardiovascular adverse events including QT-interval prolongation and heart failure. However, they have not been predicted by preclinical studies. Hence, a new method to assess the tyrosine kinase inhibitor-induced adverse effects needs to be established. Here, we intravenously administered lapatinib to halothane-anaesthetised dogs, evaluating cardiohemodynamic, electrophysiological, and echocardiographic profiles for pharmacological safety assessments. We intravenously administered lapatinib to chronic atrioventricular block beagle dogs to assess its proarrhythmic potential. The therapeutic concentration of lapatinib significantly increased total peripheral vascular resistance, QT, QTc, monophasic action potential (MAP)(90(sinus),) MAP(90(CL400)), effective refractory period, and plasma concentration of cardiac troponin I (cTnI), suggesting that lapatinib prolonged the ventricular repolarization without inducing lethal ventricular arrhythmia. Careful monitoring of plasma cTnI concentration and an electrocardiogram could be supportive biomarkers, predicting the onset of lapatinib-induced cardiovascular adverse events. |
format | Online Article Text |
id | pubmed-6971088 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-69710882020-01-27 Precise safety pharmacology studies of lapatinib for onco-cardiology assessed using in vivo canine models Ando, Kentaro Wada, Takeshi Cao, Xin Sci Rep Article Cancer chemotherapies have improved prognosis in cancer patients, resulting in a large and rapidly increasing number of cancer survivors. “Onco-cardiology” or “cardio-oncology” is a new discipline for addressing the unanticipated cardiac side effects of newly developed cancer drugs. Lapatinib, a tyrosine kinase inhibitor suppressing the epidermal growth factor receptor and ErbB2, has been used in advanced or metastatic breast cancer treatment. Reportedly, lapatinib has induced cardiovascular adverse events including QT-interval prolongation and heart failure. However, they have not been predicted by preclinical studies. Hence, a new method to assess the tyrosine kinase inhibitor-induced adverse effects needs to be established. Here, we intravenously administered lapatinib to halothane-anaesthetised dogs, evaluating cardiohemodynamic, electrophysiological, and echocardiographic profiles for pharmacological safety assessments. We intravenously administered lapatinib to chronic atrioventricular block beagle dogs to assess its proarrhythmic potential. The therapeutic concentration of lapatinib significantly increased total peripheral vascular resistance, QT, QTc, monophasic action potential (MAP)(90(sinus),) MAP(90(CL400)), effective refractory period, and plasma concentration of cardiac troponin I (cTnI), suggesting that lapatinib prolonged the ventricular repolarization without inducing lethal ventricular arrhythmia. Careful monitoring of plasma cTnI concentration and an electrocardiogram could be supportive biomarkers, predicting the onset of lapatinib-induced cardiovascular adverse events. Nature Publishing Group UK 2020-01-20 /pmc/articles/PMC6971088/ /pubmed/31959820 http://dx.doi.org/10.1038/s41598-020-57601-x Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Ando, Kentaro Wada, Takeshi Cao, Xin Precise safety pharmacology studies of lapatinib for onco-cardiology assessed using in vivo canine models |
title | Precise safety pharmacology studies of lapatinib for onco-cardiology assessed using in vivo canine models |
title_full | Precise safety pharmacology studies of lapatinib for onco-cardiology assessed using in vivo canine models |
title_fullStr | Precise safety pharmacology studies of lapatinib for onco-cardiology assessed using in vivo canine models |
title_full_unstemmed | Precise safety pharmacology studies of lapatinib for onco-cardiology assessed using in vivo canine models |
title_short | Precise safety pharmacology studies of lapatinib for onco-cardiology assessed using in vivo canine models |
title_sort | precise safety pharmacology studies of lapatinib for onco-cardiology assessed using in vivo canine models |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971088/ https://www.ncbi.nlm.nih.gov/pubmed/31959820 http://dx.doi.org/10.1038/s41598-020-57601-x |
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