Document Detail


Female sex and drug dose as risk factors for late cardiotoxic effects of doxorubicin therapy for childhood cancer.
MedLine Citation:
PMID:  7760889     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The New England journal of medicine     Volume:  332     ISSN:  0028-4793     ISO Abbreviation:  N. Engl. J. Med.     Publication Date:  1995 Jun 
Date Detail:
Created Date:  1995-06-29     Completed Date:  1995-06-29     Revised Date:  2010-03-24    
Medline Journal Info:
Nlm Unique ID:  0255562     Medline TA:  N Engl J Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1738-43     Citation Subset:  AIM; IM    
Affiliation:
Department of Cardiology, Children's Hospital, Boston, MA 02115, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
CA06516/CA/NCI NIH HHS; CA34183/CA/NCI NIH HHS; CA55576/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
23214-92-8/Doxorubicin
Comments/Corrections
Comment In:
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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