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    Effects of dexrazoxane on doxorubicin-related cardiotoxicity and second malignant neoplasms in children with osteosarcoma: a report from the Children’s Oncology Group

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    Author
    Kopp, Lisa M.
    Womer, Richard B.
    Schwartz, Cindy L.
    Ebb, David H.
    Franco, Vivian I.
    Hall, David
    Barkauskas, Donald A.
    Krailo, Mark D.
    Grier, Holcombe E.
    Meyers, Paul A.
    Wexler, Leonard H.
    Marina, Neyssa M.
    Janeway, Katherine A.
    Gorlick, Richard
    Bernstein, Mark L.
    Lipshultz, Steven E.
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    Affiliation
    Univ Arizona
    Issue Date
    2019-10-09
    
    Metadata
    Show full item record
    Publisher
    BMC
    Citation
    Kopp, L.M., Womer, R.B., Schwartz, C.L. et al. Effects of dexrazoxane on doxorubicin-related cardiotoxicity and second malignant neoplasms in children with osteosarcoma: a report from the Children’s Oncology Group. Cardio-Oncology 5, 15 (2019) doi:10.1186/s40959-019-0050-9
    Journal
    Cardio-Oncology
    Rights
    © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
    Collection Information
    This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
    Abstract
    Background: Dexrazoxane protects from lower-cumulative-dose doxorubicin cardiotoxicity, but the effect of dexrazoxane in children with sarcoma treated with higher-cumulative-dose doxorubicin is unknown. Methods: We evaluated children with osteosarcoma (OS) on two Children’s Oncology Group trials with higher dose doxorubicin (375–600 mg/m2) preceded by dexrazoxane (10:1 dexrazoxane:doxorubicin dosing). They were evaluated after the minimum expected treatment time (METT), defined as 28 weeks. Cardiotoxicity was identified by echocardiography and serum N-terminal pro-brain natriuretic peptide (NT-proBNP). Second malignant neoplasm (SMN) data was collected. Results: All children had normal left ventricular (LV) systolic function as measured by LV fractional shortening and no heart failure. The end-diastolic septal thickness Z-scores (P < 0.01) and LV mass Z-scores (P < 0.01) were significantly smaller than normal for body-surface area in both sexes. The average LV mass Z-scores were significantly smaller for girls (P < 0.01) and marginally smaller for boys (P = 0.06). Girls had significantly smaller LV end-diastolic dimension Z-scores normalized to BSA (P < 0.01) compared to healthy controls and had significant increases in NT-proBNP. Four children developed SMNs as first events, a rate similar to historical controls. Conclusions: Dexrazoxane prevented LV dysfunction and heart failure in children with OS receiving higher dose doxorubicin. However, LV structural changes were not fully prevented, especially in girls. As a result, hearts become abnormally small for body size, resulting in higher LV stress. Dexrazoxane did not increase the risk of SMN. Dexrazoxane should be used in this population, particularly for girls, to mitigate anthracycline-induced cardiotoxicity.
    Note
    Open access journal
    ISSN
    2057-3804
    DOI
    10.1186/s40959-019-0050-9
    Version
    Final published version
    ae974a485f413a2113503eed53cd6c53
    10.1186/s40959-019-0050-9
    Scopus Count
    Collections
    UA Faculty Publications

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