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Evaluation of cardiac safety of lapatinib therapy for ErbB2-positive metastatic breast cancer: A single center experience
Lapatinib is a dual tyrosine kinase inhibitor (TKI) that has a considerable efficacy in ErbB2-positive metastatic breast cancer (MBC). Previous studies revealed that TKIs caused cardiotoxicity in approximately 10 % of the patients. This study assessed the cardiac safety of lapatinib in women with Er...
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| Published in: | Medical oncology (Northwood, London, England) London, England), 2012-12, Vol.29 (5), p.3232-3239 |
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| creator | Dogan, Erkan Yorgun, Hikmet Petekkaya, Ibrahim Ozer, Necla Altundag, Kadri Ozisik, Yavuz |
| description | Lapatinib is a dual tyrosine kinase inhibitor (TKI) that has a considerable efficacy in ErbB2-positive metastatic breast cancer (MBC). Previous studies revealed that TKIs caused cardiotoxicity in approximately 10 % of the patients. This study assessed the cardiac safety of lapatinib in women with ErbB2-positive MBC. In this observational single center study, all patients with ErbB2-positive MBC who were previously treated with anthracycline, taxanes, and trastuzumab in the adjuvant and/or metastatic setting were assigned to receive lapatinib at a dose of 1,250 mg per day continuously plus capecitabine at a dose of 2,000 mg/m
2
in two divided doses on days 1 through 14 of a 21-day cycle. Cardiac toxicity was assessed with symptoms, transthoracic echocardiography, electrocardiography and biochemical markers (brain natriuretic peptide (BNP), creatine kinase (CK) and creatine kinase-MB) at baseline and every 9 weeks until disease progression. Twenty-six patients were treated with lapatinib and capecitabine therapy for a median of 18 (range 3–60) weeks. The median age was 48 (range 28–83) years. All patients had ErbB2-positive MBC. Among 25 eligible patients, 5 (19.2 %) patients experienced new cardiac events compared with baseline findings. Of these 5 patients, 1 (3.8 %) had
T
wave negativity, 1 (3.8 %) had sinus tachycardia, 1 (3.8 %) had grade 1 (453 ms) QT prolongation, and 2 (7.7 %) had decreased LVEF below the critical level. Among eligible 21 patients, 2 (7.7 %) had increased BNP, 1 (3.8 %) had increased CK, and 1 (3.8 %) had increased CK–MB level compared with baseline. No serious cardiac events that required monitorization or medication occurred. There was no statistically significant relationship between the duration of lapatinib administration and LVEF changes, QT prolongation, BNP, CK, and CK–MB level. According to our findings, lapatinib was safe and well tolerated and has a low incidence of cardiac side effects. Therefore, it seemed that cardiotoxicity was not a class effect of TKIs. However, despite the absence of clinically significant adverse cardiac effects under lapatinib therapy, the incidence of cardiotoxicity reported in our study was higher than previous lapatinib studies. |
| doi_str_mv | 10.1007/s12032-012-0253-5 |
| format | article |
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2
in two divided doses on days 1 through 14 of a 21-day cycle. Cardiac toxicity was assessed with symptoms, transthoracic echocardiography, electrocardiography and biochemical markers (brain natriuretic peptide (BNP), creatine kinase (CK) and creatine kinase-MB) at baseline and every 9 weeks until disease progression. Twenty-six patients were treated with lapatinib and capecitabine therapy for a median of 18 (range 3–60) weeks. The median age was 48 (range 28–83) years. All patients had ErbB2-positive MBC. Among 25 eligible patients, 5 (19.2 %) patients experienced new cardiac events compared with baseline findings. Of these 5 patients, 1 (3.8 %) had
T
wave negativity, 1 (3.8 %) had sinus tachycardia, 1 (3.8 %) had grade 1 (453 ms) QT prolongation, and 2 (7.7 %) had decreased LVEF below the critical level. Among eligible 21 patients, 2 (7.7 %) had increased BNP, 1 (3.8 %) had increased CK, and 1 (3.8 %) had increased CK–MB level compared with baseline. No serious cardiac events that required monitorization or medication occurred. There was no statistically significant relationship between the duration of lapatinib administration and LVEF changes, QT prolongation, BNP, CK, and CK–MB level. According to our findings, lapatinib was safe and well tolerated and has a low incidence of cardiac side effects. Therefore, it seemed that cardiotoxicity was not a class effect of TKIs. However, despite the absence of clinically significant adverse cardiac effects under lapatinib therapy, the incidence of cardiotoxicity reported in our study was higher than previous lapatinib studies.</description><identifier>ISSN: 1357-0560</identifier><identifier>EISSN: 1559-131X</identifier><identifier>DOI: 10.1007/s12032-012-0253-5</identifier><identifier>PMID: 22729366</identifier><identifier>CODEN: MONCEZ</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents - adverse effects ; Breast cancer ; Breast Neoplasms - drug therapy ; Breast Neoplasms - pathology ; Female ; Genes, erbB-2 ; Heart - drug effects ; Heart Diseases - chemically induced ; Heart Diseases - epidemiology ; Hematology ; Humans ; Incidence ; Internal Medicine ; Medicine ; Medicine & Public Health ; Middle Aged ; Oncology ; Original Paper ; Pathology ; Quinazolines - adverse effects ; Receptor, ErbB-2 - antagonists & inhibitors</subject><ispartof>Medical oncology (Northwood, London, England), 2012-12, Vol.29 (5), p.3232-3239</ispartof><rights>Springer Science+Business Media, LLC 2012</rights><rights>Springer Science+Business Media New York 2012</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-217bb926182be225bd54bc3850e85ab4a96d443a6afe2cf19e390bc63f8573a3</citedby><cites>FETCH-LOGICAL-c372t-217bb926182be225bd54bc3850e85ab4a96d443a6afe2cf19e390bc63f8573a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22729366$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dogan, Erkan</creatorcontrib><creatorcontrib>Yorgun, Hikmet</creatorcontrib><creatorcontrib>Petekkaya, Ibrahim</creatorcontrib><creatorcontrib>Ozer, Necla</creatorcontrib><creatorcontrib>Altundag, Kadri</creatorcontrib><creatorcontrib>Ozisik, Yavuz</creatorcontrib><title>Evaluation of cardiac safety of lapatinib therapy for ErbB2-positive metastatic breast cancer: A single center experience</title><title>Medical oncology (Northwood, London, England)</title><addtitle>Med Oncol</addtitle><addtitle>Med Oncol</addtitle><description>Lapatinib is a dual tyrosine kinase inhibitor (TKI) that has a considerable efficacy in ErbB2-positive metastatic breast cancer (MBC). Previous studies revealed that TKIs caused cardiotoxicity in approximately 10 % of the patients. This study assessed the cardiac safety of lapatinib in women with ErbB2-positive MBC. In this observational single center study, all patients with ErbB2-positive MBC who were previously treated with anthracycline, taxanes, and trastuzumab in the adjuvant and/or metastatic setting were assigned to receive lapatinib at a dose of 1,250 mg per day continuously plus capecitabine at a dose of 2,000 mg/m
2
in two divided doses on days 1 through 14 of a 21-day cycle. Cardiac toxicity was assessed with symptoms, transthoracic echocardiography, electrocardiography and biochemical markers (brain natriuretic peptide (BNP), creatine kinase (CK) and creatine kinase-MB) at baseline and every 9 weeks until disease progression. Twenty-six patients were treated with lapatinib and capecitabine therapy for a median of 18 (range 3–60) weeks. The median age was 48 (range 28–83) years. All patients had ErbB2-positive MBC. Among 25 eligible patients, 5 (19.2 %) patients experienced new cardiac events compared with baseline findings. Of these 5 patients, 1 (3.8 %) had
T
wave negativity, 1 (3.8 %) had sinus tachycardia, 1 (3.8 %) had grade 1 (453 ms) QT prolongation, and 2 (7.7 %) had decreased LVEF below the critical level. Among eligible 21 patients, 2 (7.7 %) had increased BNP, 1 (3.8 %) had increased CK, and 1 (3.8 %) had increased CK–MB level compared with baseline. No serious cardiac events that required monitorization or medication occurred. There was no statistically significant relationship between the duration of lapatinib administration and LVEF changes, QT prolongation, BNP, CK, and CK–MB level. According to our findings, lapatinib was safe and well tolerated and has a low incidence of cardiac side effects. Therefore, it seemed that cardiotoxicity was not a class effect of TKIs. 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Yorgun, Hikmet ; Petekkaya, Ibrahim ; Ozer, Necla ; Altundag, Kadri ; Ozisik, Yavuz</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c372t-217bb926182be225bd54bc3850e85ab4a96d443a6afe2cf19e390bc63f8573a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antineoplastic Agents - adverse effects</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - pathology</topic><topic>Female</topic><topic>Genes, erbB-2</topic><topic>Heart - drug effects</topic><topic>Heart Diseases - chemically induced</topic><topic>Heart Diseases - epidemiology</topic><topic>Hematology</topic><topic>Humans</topic><topic>Incidence</topic><topic>Internal Medicine</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Oncology</topic><topic>Original Paper</topic><topic>Pathology</topic><topic>Quinazolines - adverse effects</topic><topic>Receptor, ErbB-2 - antagonists & inhibitors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dogan, Erkan</creatorcontrib><creatorcontrib>Yorgun, Hikmet</creatorcontrib><creatorcontrib>Petekkaya, Ibrahim</creatorcontrib><creatorcontrib>Ozer, Necla</creatorcontrib><creatorcontrib>Altundag, Kadri</creatorcontrib><creatorcontrib>Ozisik, Yavuz</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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</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>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical 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><jtitle>Medical oncology (Northwood, London, England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dogan, Erkan</au><au>Yorgun, Hikmet</au><au>Petekkaya, Ibrahim</au><au>Ozer, Necla</au><au>Altundag, Kadri</au><au>Ozisik, Yavuz</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of cardiac safety of lapatinib therapy for ErbB2-positive metastatic breast cancer: A single center experience</atitle><jtitle>Medical oncology (Northwood, London, England)</jtitle><stitle>Med Oncol</stitle><addtitle>Med Oncol</addtitle><date>2012-12-01</date><risdate>2012</risdate><volume>29</volume><issue>5</issue><spage>3232</spage><epage>3239</epage><pages>3232-3239</pages><issn>1357-0560</issn><eissn>1559-131X</eissn><coden>MONCEZ</coden><abstract>Lapatinib is a dual tyrosine kinase inhibitor (TKI) that has a considerable efficacy in ErbB2-positive metastatic breast cancer (MBC). Previous studies revealed that TKIs caused cardiotoxicity in approximately 10 % of the patients. This study assessed the cardiac safety of lapatinib in women with ErbB2-positive MBC. In this observational single center study, all patients with ErbB2-positive MBC who were previously treated with anthracycline, taxanes, and trastuzumab in the adjuvant and/or metastatic setting were assigned to receive lapatinib at a dose of 1,250 mg per day continuously plus capecitabine at a dose of 2,000 mg/m
2
in two divided doses on days 1 through 14 of a 21-day cycle. Cardiac toxicity was assessed with symptoms, transthoracic echocardiography, electrocardiography and biochemical markers (brain natriuretic peptide (BNP), creatine kinase (CK) and creatine kinase-MB) at baseline and every 9 weeks until disease progression. Twenty-six patients were treated with lapatinib and capecitabine therapy for a median of 18 (range 3–60) weeks. The median age was 48 (range 28–83) years. All patients had ErbB2-positive MBC. Among 25 eligible patients, 5 (19.2 %) patients experienced new cardiac events compared with baseline findings. Of these 5 patients, 1 (3.8 %) had
T
wave negativity, 1 (3.8 %) had sinus tachycardia, 1 (3.8 %) had grade 1 (453 ms) QT prolongation, and 2 (7.7 %) had decreased LVEF below the critical level. Among eligible 21 patients, 2 (7.7 %) had increased BNP, 1 (3.8 %) had increased CK, and 1 (3.8 %) had increased CK–MB level compared with baseline. No serious cardiac events that required monitorization or medication occurred. There was no statistically significant relationship between the duration of lapatinib administration and LVEF changes, QT prolongation, BNP, CK, and CK–MB level. According to our findings, lapatinib was safe and well tolerated and has a low incidence of cardiac side effects. Therefore, it seemed that cardiotoxicity was not a class effect of TKIs. However, despite the absence of clinically significant adverse cardiac effects under lapatinib therapy, the incidence of cardiotoxicity reported in our study was higher than previous lapatinib studies.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>22729366</pmid><doi>10.1007/s12032-012-0253-5</doi><tpages>8</tpages></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Antineoplastic Agents - adverse effects Breast cancer Breast Neoplasms - drug therapy Breast Neoplasms - pathology Female Genes, erbB-2 Heart - drug effects Heart Diseases - chemically induced Heart Diseases - epidemiology Hematology Humans Incidence Internal Medicine Medicine Medicine & Public Health Middle Aged Oncology Original Paper Pathology Quinazolines - adverse effects Receptor, ErbB-2 - antagonists & inhibitors |
| title | Evaluation of cardiac safety of lapatinib therapy for ErbB2-positive metastatic breast cancer: A single center experience |
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