| Reversibility of trastuzumab-related cardiotoxicity: new insights based on clinical course and response to medical treatment. | |
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MedLine Citation:
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PMID: 16258084 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: Trastuzumab is an important biologic agent with significant activity in breast cancers that overexpress the HER2/neu marker. However, trastuzumab is associated with cardiotoxicity that has not yet been fully explored. We present our experience with patients who developed trastuzumab-related cardiotoxicity. PATIENTS AND METHODS: Over a 4-year period, 38 patients with HER2/neu-positive breast cancer were referred for suspected trastuzumab-related cardiotoxicity. All patients had previously received anthracycline-based chemotherapy. Results After doxorubicin but before trastuzumab, the mean (+/- standard deviation) left ventricular ejection fraction (LVEF) was 0.61 +/- 0.13, and the LVEF decreased to 0.43 +/- 0.16 after trastuzumab (P < .0001). After withdrawal of trastuzumab, the LVEF increased to 0.56 +/- 0.11. Mean time to recovery of LVEF was 1.5 months and was temporally associated with medical treatment in 32 (84%) of the 38 patients but occurred without treatment in six patients (16%). Increases in LVEF were noted in 37 of the 38 patients. Twenty-five of these patients were re-treated with trastuzumab; three patients had recurrent left ventricular dysfunction, but 22 patients (88%) did not. All re-treatment patients continued on their therapeutic regimen for heart failure when rechallenged with trastuzumab. Nine patients underwent endomyocardial biopsy. Ultrastructural changes were not seen. CONCLUSION: Patients who develop cardiotoxicity while receiving trastuzumab therapy generally improve on removal of the agent. The mechanism of trastuzumab-related cardiac dysfunction is different from that of anthracycline cardiotoxicity, in part, demonstrated by the absence of anthracycline-like ultrastructural changes. Reintroducing trastuzumab may be appropriate for some individuals who previously have experienced trastuzumab-related cardiac dysfunction. |
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Authors:
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Michael S Ewer; Mary T Vooletich; Jean-Bernard Durand; Myrshia L Woods; Joseph R Davis; Vicente Valero; Daniel J Lenihan |
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Publication Detail:
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Type: Comparative Study; Journal Article |
Journal Detail:
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Title: Journal of clinical oncology : official journal of the American Society of Clinical Oncology Volume: 23 ISSN: 0732-183X ISO Abbreviation: J. Clin. Oncol. Publication Date: 2005 Nov |
Date Detail:
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Created Date: 2005-10-31 Completed Date: 2005-12-09 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 8309333 Medline TA: J Clin Oncol Country: United States |
Other Details:
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Languages: eng Pagination: 7820-6 Citation Subset: IM |
Affiliation:
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Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, 77030, USA. mewer@mdanderson.org |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Anthracyclines / administration & dosage Antibodies, Monoclonal / administration & dosage, adverse effects* Antineoplastic Combined Chemotherapy Protocols / adverse effects* Breast Neoplasms / drug therapy* Doxorubicin / administration & dosage Female Heart / drug effects* Heart Failure / chemically induced*, drug therapy Humans Middle Aged Receptor, erbB-2 / metabolism* Retrospective Studies Treatment Outcome Ventricular Dysfunction, Left / chemically induced*, drug therapy |
| Chemical | |
Reg. No./Substance:
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0/Anthracyclines; 0/Antibodies, Monoclonal; 0/trastuzumab; 23214-92-8/Doxorubicin; EC 2.7.10.1/Receptor, erbB-2 |
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