| Female sex and drug dose as risk factors for late cardiotoxic effects of doxorubicin therapy for childhood cancer. | |
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MedLine Citation:
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PMID: 7760889 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Late cardiotoxic effects of doxorubicin are increasingly a problem for patients who survive childhood cancer. Cardiotoxicity is often progressive, and some patients have disabling symptoms. Our objective was to identify risk factors for late cardiotoxicity. METHODS: We examined echocardiograms from 120 children and adults who had received cumulative doses of 244 to 550 mg of doxorubicin per square meter of body-surface area for the treatment of acute lymphoblastic leukemia or osteogenic sarcoma in childhood, a mean of 8.1 years earlier. Measurements of blood pressure and left ventricular function, contractility (measured as the stress-velocity index), end-diastolic posterior-wall thickness, end-diastolic dimension, mass, and afterload (measured as end-systolic wall stress) were compared with sex-specific values from a cohort of 296 normal subjects. RESULTS: All echocardiographic measurements were abnormal at follow-up a minimum of two years after the end of therapy, with more frequent and severe abnormalities in female patients. In a multivariate analysis, female sex and a higher cumulative dose of doxorubicin were associated with depressed contractility (P < or = 0.001), and there was an interaction between these two variables. Independent and significant associations were found between a higher rate of administration of doxorubicin and increased afterload (P < or = 0.001), left ventricular dilatation, and depressed left ventricular function; between a higher cumulative dose and depressed left ventricular function (P < or = 0.001); between a younger age at diagnosis and reduced left-ventricular-wall thickness and mass and increased afterload; and between a longer time since the completion of doxorubicin therapy and reduced left-ventricular-wall thickness and increased afterload (P < or = 0.001). CONCLUSIONS: Female sex and a higher rate of administration of doxorubicin were independent risk factors for cardiac abnormalities after treatment with doxorubicin for childhood cancer; the prevalence and severity of abnormalities increased with longer follow-up. |
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Authors:
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S E Lipshultz; S R Lipsitz; S M Mone; A M Goorin; S E Sallan; S P Sanders; E J Orav; R D Gelber; S D Colan |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The New England journal of medicine Volume: 332 ISSN: 0028-4793 ISO Abbreviation: N. Engl. J. Med. Publication Date: 1995 Jun |
Date Detail:
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Created Date: 1995-06-29 Completed Date: 1995-06-29 Revised Date: 2010-03-24 |
Medline Journal Info:
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Nlm Unique ID: 0255562 Medline TA: N Engl J Med Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1738-43 Citation Subset: AIM; IM |
Affiliation:
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Department of Cardiology, Children's Hospital, Boston, MA 02115, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Age of Onset Analysis of Variance Child Child, Preschool Doxorubicin / administration & dosage, adverse effects* Female Follow-Up Studies Heart Diseases / chemically induced*, ultrasonography Humans Infant Male Myocardial Contraction / drug effects Osteosarcoma / drug therapy Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy Risk Factors Sex Factors Survivors Ventricular Function, Left / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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CA06516/CA/NCI NIH HHS; CA34183/CA/NCI NIH HHS; CA55576/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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23214-92-8/Doxorubicin |
| Comments/Corrections | |
Comment In:
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N Engl J Med. 1995 Nov 16;333(20):1359-60
[PMID:
7566043
]
N Engl J Med. 1995 Nov 16;333(20):1360 [PMID: 7566044 ] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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