Female sex and higher drug dose as risk factors for late cardiotoxic effects of doxorubicin therapy for childhood cancer

Steven 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

Research output: Contribution to journalArticle

600 Citations (Scopus)

Abstract

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≤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≤0.001), left ventricular dilatation, and depressed left ventricular function; between a higher cumulative dose and depressed left ventricular function (P≤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≤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.

Original languageEnglish
Pages (from-to)1738-1743
Number of pages6
JournalNew England Journal of Medicine
Volume332
Issue number26
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

Fingerprint

Doxorubicin
Pharmaceutical Preparations
Left Ventricular Function
Neoplasms
Therapeutics
Body Surface Area
Osteosarcoma
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Dilatation
Multivariate Analysis
Blood Pressure

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Lipshultz, S. E., Lipsitz, S. R., Mone, S. M., Goorin, A. M., Sallan, S. E., Sanders, S. P., ... Colan, S. D. (1995). Female sex and higher drug dose as risk factors for late cardiotoxic effects of doxorubicin therapy for childhood cancer. New England Journal of Medicine, 332(26), 1738-1743. https://doi.org/10.1056/NEJM199506293322602

Female sex and higher drug dose as risk factors for late cardiotoxic effects of doxorubicin therapy for childhood cancer. / Lipshultz, Steven E; Lipsitz, S. R.; Mone, S. M.; Goorin, A. M.; Sallan, S. E.; Sanders, S. P.; Orav, E. J.; Gelber, R. D.; Colan, S. D.

In: New England Journal of Medicine, Vol. 332, No. 26, 01.01.1995, p. 1738-1743.

Research output: Contribution to journalArticle

Lipshultz, SE, Lipsitz, SR, Mone, SM, Goorin, AM, Sallan, SE, Sanders, SP, Orav, EJ, Gelber, RD & Colan, SD 1995, 'Female sex and higher drug dose as risk factors for late cardiotoxic effects of doxorubicin therapy for childhood cancer', New England Journal of Medicine, vol. 332, no. 26, pp. 1738-1743. https://doi.org/10.1056/NEJM199506293322602
Lipshultz, Steven E ; Lipsitz, S. R. ; Mone, S. M. ; Goorin, A. M. ; Sallan, S. E. ; Sanders, S. P. ; Orav, E. J. ; Gelber, R. D. ; Colan, S. D. / Female sex and higher drug dose as risk factors for late cardiotoxic effects of doxorubicin therapy for childhood cancer. In: New England Journal of Medicine. 1995 ; Vol. 332, No. 26. pp. 1738-1743.
@article{4ef282cefe7444ed895dbcda5f611c0c,
title = "Female sex and higher drug dose as risk factors for late cardiotoxic effects of doxorubicin therapy for childhood cancer",
abstract = "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≤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≤0.001), left ventricular dilatation, and depressed left ventricular function; between a higher cumulative dose and depressed left ventricular function (P≤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≤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.",
author = "Lipshultz, {Steven E} and Lipsitz, {S. R.} and Mone, {S. M.} and Goorin, {A. M.} and Sallan, {S. E.} and Sanders, {S. P.} and Orav, {E. J.} and Gelber, {R. D.} and Colan, {S. D.}",
year = "1995",
month = "1",
day = "1",
doi = "10.1056/NEJM199506293322602",
language = "English",
volume = "332",
pages = "1738--1743",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "26",

}

TY - JOUR

T1 - Female sex and higher drug dose as risk factors for late cardiotoxic effects of doxorubicin therapy for childhood cancer

AU - Lipshultz, Steven E

AU - Lipsitz, S. R.

AU - Mone, S. M.

AU - Goorin, A. M.

AU - Sallan, S. E.

AU - Sanders, S. P.

AU - Orav, E. J.

AU - Gelber, R. D.

AU - Colan, S. D.

PY - 1995/1/1

Y1 - 1995/1/1

N2 - 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≤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≤0.001), left ventricular dilatation, and depressed left ventricular function; between a higher cumulative dose and depressed left ventricular function (P≤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≤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.

AB - 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≤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≤0.001), left ventricular dilatation, and depressed left ventricular function; between a higher cumulative dose and depressed left ventricular function (P≤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≤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.

UR - http://www.scopus.com/inward/record.url?scp=0028989408&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028989408&partnerID=8YFLogxK

U2 - 10.1056/NEJM199506293322602

DO - 10.1056/NEJM199506293322602

M3 - Article

C2 - 7760889

AN - SCOPUS:0028989408

VL - 332

SP - 1738

EP - 1743

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 26

ER -