Late Mortality After Dexrazoxane Treatment: A Report From the Children's Oncology Group

Eric J Chow; Barbara L Asselin; Cindy L Schwartz; David R Doody; Wendy M Leisenring; Sanjeev Aggarwal; K Scott Baker; Smita Bhatia; Louis S Constine; David R Freyer; Steven E Lipshultz; Saro H Armenian

doi:10.1200/JCO.2014.59.4473

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Late Mortality After Dexrazoxane Treatment: A Report From the Children's Oncology Group

Journal article

Open access

Peer reviewed

Late Mortality After Dexrazoxane Treatment: A Report From the Children's Oncology Group

Eric J Chow, Barbara L Asselin, Cindy L Schwartz, David R Doody, Wendy M Leisenring, Sanjeev Aggarwal, K Scott Baker, Smita Bhatia, Louis S Constine, David R Freyer, …

Journal of clinical oncology, Vol.33(24), pp.2639-2645

2015-08-20

DOI: https://doi.org/10.1200/JCO.2014.59.4473

PMCID: PMC4534526

PMID: 26014292

Abstract

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - drug therapy

Antineoplastic Combined Chemotherapy Protocols - administration & dosage

Humans

Antineoplastic Combined Chemotherapy Protocols - adverse effects

Child, Preschool

Infant

Male

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - mortality

Dexrazoxane - administration & dosage

Young Adult

Drug Interactions

Adolescent

Dexrazoxane - adverse effects

Hodgkin Disease - drug therapy

Hodgkin Disease - mortality

Adult

Female

Child

Doxorubicin - administration & dosage

Given concerns that dexrazoxane may reduce treatment efficacy, induce second cancers, and thus compromise overall survival among children, we examined long-term overall and cause-specific mortality and disease relapse rates from three randomized clinical trials. Children's Oncology Group trials P9404 (T-cell acute lymphoblastic leukemia/lymphoma; n = 537), P9425 (intermediate/high-risk Hodgkin lymphoma; n = 216), and P9426 (low-risk Hodgkin lymphoma; n = 255) were conducted between 1996 and 2001. Each trial randomly assigned patients to doxorubicin with or without dexrazoxane. The dexrazoxane:doxorubicin dose ratio was 10:1, and the cumulative protocol-specified doxorubicin dose was 100 to 360 mg/m(2). Dexrazoxane was given as an intravenous bolus before each doxorubicin dose. Data from all three trials were linked with the National Death Index to determine overall and cause-specific mortality by dexrazoxane status. Among 1,008 patients (507 received dexrazoxane) with a median follow-up of 12.6 years (range, 0 to 15.5 years), 132 died (67 received dexrazoxane). Overall mortality did not vary by dexrazoxane status (12.8% with dexrazoxane at 10 years v 12.2% without; hazard ratio [HR], 1.03; 95% CI, 0.73 to 1.45). Findings were similar when each trial was examined separately. Dexrazoxane also was not significantly associated with differential causes of death. The original cancer caused 76.5% of all deaths (HR, 0.90; 95% CI, 0.61 to 1.32) followed by second cancers (13.6% of deaths; HR, 1.24; 95% CI, 0.49 to 3.15). Specifically, dexrazoxane was not associated with deaths from acute myeloid leukemia/myelodysplasia or cardiovascular events. Among pediatric patients with leukemia or lymphoma, after extended follow-up, dexrazoxane use did not seem to compromise long-term survival.

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.219 Cancer Drugs; 1.219.1342 Cardiotoxicity
Web Of Science research areas: Oncology
ESI research areas: Clinical Medicine

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Title: Late Mortality After Dexrazoxane Treatment: A Report From the Children's Oncology Group
Creators: Eric J Chow - Eric J. Chow, David R. Doody, Wendy M. Leisenring, and K. Scott Baker, Fred Hutchinson Cancer Research Center, Seattle Children's Hospital, University of Washington, Seattle, WA; Barbara L. Asselin and Louis S. Constine, University of Rochester Medical Center and School of Medicine, Rochester, NY; Cindy L. Schwartz, University of Texas MD Anderson Cancer Center, Houston, TX; Sanjeev Aggarwal and Steven E. Lipshultz, Children's Hospital of Michigan, Wayne State University, Detroit, MI; Smita Bhatia, University of Alabama, Birmingham, AL; David R. Freyer, Children's Hospital Los Angeles, University of Southern California, Los Angeles; and Saro H. Armenian, City of Hope Cancer Center, Duarte, CA. ericchow@u.washington.edu
Barbara L Asselin - Eric J. Chow, David R. Doody, Wendy M. Leisenring, and K. Scott Baker, Fred Hutchinson Cancer Research Center, Seattle Children's Hospital, University of Washington, Seattle, WA; Barbara L. Asselin and Louis S. Constine, University of Rochester Medical Center and School of Medicine, Rochester, NY; Cindy L. Schwartz, University of Texas MD Anderson Cancer Center, Houston, TX; Sanjeev Aggarwal and Steven E. Lipshultz, Children's Hospital of Michigan, Wayne State University, Detroit, MI; Smita Bhatia, University of Alabama, Birmingham, AL; David R. Freyer, Children's Hospital Los Angeles, University of Southern California, Los Angeles; and Saro H. Armenian, City of Hope Cancer Center, Duarte, CA
Cindy L Schwartz - Eric J. Chow, David R. Doody, Wendy M. Leisenring, and K. Scott Baker, Fred Hutchinson Cancer Research Center, Seattle Children's Hospital, University of Washington, Seattle, WA; Barbara L. Asselin and Louis S. Constine, University of Rochester Medical Center and School of Medicine, Rochester, NY; Cindy L. Schwartz, University of Texas MD Anderson Cancer Center, Houston, TX; Sanjeev Aggarwal and Steven E. Lipshultz, Children's Hospital of Michigan, Wayne State University, Detroit, MI; Smita Bhatia, University of Alabama, Birmingham, AL; David R. Freyer, Children's Hospital Los Angeles, University of Southern California, Los Angeles; and Saro H. Armenian, City of Hope Cancer Center, Duarte, CA
David R Doody - Eric J. Chow, David R. Doody, Wendy M. Leisenring, and K. Scott Baker, Fred Hutchinson Cancer Research Center, Seattle Children's Hospital, University of Washington, Seattle, WA; Barbara L. Asselin and Louis S. Constine, University of Rochester Medical Center and School of Medicine, Rochester, NY; Cindy L. Schwartz, University of Texas MD Anderson Cancer Center, Houston, TX; Sanjeev Aggarwal and Steven E. Lipshultz, Children's Hospital of Michigan, Wayne State University, Detroit, MI; Smita Bhatia, University of Alabama, Birmingham, AL; David R. Freyer, Children's Hospital Los Angeles, University of Southern California, Los Angeles; and Saro H. Armenian, City of Hope Cancer Center, Duarte, CA
Wendy M Leisenring - Eric J. Chow, David R. Doody, Wendy M. Leisenring, and K. Scott Baker, Fred Hutchinson Cancer Research Center, Seattle Children's Hospital, University of Washington, Seattle, WA; Barbara L. Asselin and Louis S. Constine, University of Rochester Medical Center and School of Medicine, Rochester, NY; Cindy L. Schwartz, University of Texas MD Anderson Cancer Center, Houston, TX; Sanjeev Aggarwal and Steven E. Lipshultz, Children's Hospital of Michigan, Wayne State University, Detroit, MI; Smita Bhatia, University of Alabama, Birmingham, AL; David R. Freyer, Children's Hospital Los Angeles, University of Southern California, Los Angeles; and Saro H. Armenian, City of Hope Cancer Center, Duarte, CA
Sanjeev Aggarwal - Eric J. Chow, David R. Doody, Wendy M. Leisenring, and K. Scott Baker, Fred Hutchinson Cancer Research Center, Seattle Children's Hospital, University of Washington, Seattle, WA; Barbara L. Asselin and Louis S. Constine, University of Rochester Medical Center and School of Medicine, Rochester, NY; Cindy L. Schwartz, University of Texas MD Anderson Cancer Center, Houston, TX; Sanjeev Aggarwal and Steven E. Lipshultz, Children's Hospital of Michigan, Wayne State University, Detroit, MI; Smita Bhatia, University of Alabama, Birmingham, AL; David R. Freyer, Children's Hospital Los Angeles, University of Southern California, Los Angeles; and Saro H. Armenian, City of Hope Cancer Center, Duarte, CA
K Scott Baker - Eric J. Chow, David R. Doody, Wendy M. Leisenring, and K. Scott Baker, Fred Hutchinson Cancer Research Center, Seattle Children's Hospital, University of Washington, Seattle, WA; Barbara L. Asselin and Louis S. Constine, University of Rochester Medical Center and School of Medicine, Rochester, NY; Cindy L. Schwartz, University of Texas MD Anderson Cancer Center, Houston, TX; Sanjeev Aggarwal and Steven E. Lipshultz, Children's Hospital of Michigan, Wayne State University, Detroit, MI; Smita Bhatia, University of Alabama, Birmingham, AL; David R. Freyer, Children's Hospital Los Angeles, University of Southern California, Los Angeles; and Saro H. Armenian, City of Hope Cancer Center, Duarte, CA
Smita Bhatia - Eric J. Chow, David R. Doody, Wendy M. Leisenring, and K. Scott Baker, Fred Hutchinson Cancer Research Center, Seattle Children's Hospital, University of Washington, Seattle, WA; Barbara L. Asselin and Louis S. Constine, University of Rochester Medical Center and School of Medicine, Rochester, NY; Cindy L. Schwartz, University of Texas MD Anderson Cancer Center, Houston, TX; Sanjeev Aggarwal and Steven E. Lipshultz, Children's Hospital of Michigan, Wayne State University, Detroit, MI; Smita Bhatia, University of Alabama, Birmingham, AL; David R. Freyer, Children's Hospital Los Angeles, University of Southern California, Los Angeles; and Saro H. Armenian, City of Hope Cancer Center, Duarte, CA
Louis S Constine - Eric J. Chow, David R. Doody, Wendy M. Leisenring, and K. Scott Baker, Fred Hutchinson Cancer Research Center, Seattle Children's Hospital, University of Washington, Seattle, WA; Barbara L. Asselin and Louis S. Constine, University of Rochester Medical Center and School of Medicine, Rochester, NY; Cindy L. Schwartz, University of Texas MD Anderson Cancer Center, Houston, TX; Sanjeev Aggarwal and Steven E. Lipshultz, Children's Hospital of Michigan, Wayne State University, Detroit, MI; Smita Bhatia, University of Alabama, Birmingham, AL; David R. Freyer, Children's Hospital Los Angeles, University of Southern California, Los Angeles; and Saro H. Armenian, City of Hope Cancer Center, Duarte, CA
David R Freyer - Eric J. Chow, David R. Doody, Wendy M. Leisenring, and K. Scott Baker, Fred Hutchinson Cancer Research Center, Seattle Children's Hospital, University of Washington, Seattle, WA; Barbara L. Asselin and Louis S. Constine, University of Rochester Medical Center and School of Medicine, Rochester, NY; Cindy L. Schwartz, University of Texas MD Anderson Cancer Center, Houston, TX; Sanjeev Aggarwal and Steven E. Lipshultz, Children's Hospital of Michigan, Wayne State University, Detroit, MI; Smita Bhatia, University of Alabama, Birmingham, AL; David R. Freyer, Children's Hospital Los Angeles, University of Southern California, Los Angeles; and Saro H. Armenian, City of Hope Cancer Center, Duarte, CA
Steven E Lipshultz - Eric J. Chow, David R. Doody, Wendy M. Leisenring, and K. Scott Baker, Fred Hutchinson Cancer Research Center, Seattle Children's Hospital, University of Washington, Seattle, WA; Barbara L. Asselin and Louis S. Constine, University of Rochester Medical Center and School of Medicine, Rochester, NY; Cindy L. Schwartz, University of Texas MD Anderson Cancer Center, Houston, TX; Sanjeev Aggarwal and Steven E. Lipshultz, Children's Hospital of Michigan, Wayne State University, Detroit, MI; Smita Bhatia, University of Alabama, Birmingham, AL; David R. Freyer, Children's Hospital Los Angeles, University of Southern California, Los Angeles; and Saro H. Armenian, City of Hope Cancer Center, Duarte, CA
Saro H Armenian - Eric J. Chow, David R. Doody, Wendy M. Leisenring, and K. Scott Baker, Fred Hutchinson Cancer Research Center, Seattle Children's Hospital, University of Washington, Seattle, WA; Barbara L. Asselin and Louis S. Constine, University of Rochester Medical Center and School of Medicine, Rochester, NY; Cindy L. Schwartz, University of Texas MD Anderson Cancer Center, Houston, TX; Sanjeev Aggarwal and Steven E. Lipshultz, Children's Hospital of Michigan, Wayne State University, Detroit, MI; Smita Bhatia, University of Alabama, Birmingham, AL; David R. Freyer, Children's Hospital Los Angeles, University of Southern California, Los Angeles; and Saro H. Armenian, City of Hope Cancer Center, Duarte, CA
Publication Details: Journal of clinical oncology, Vol.33(24), pp.2639-2645
Publisher: United States
Grant note: K07 CA151775 / NCI NIH HHS U10 CA180886 / NCI NIH HHS U10 CA09543 / NCI NIH HHS UG1 CA189955 / NCI NIH HHS
Academic Unit: UMMG Department of Pediatrics
Language: English
Resource Type: Journal article
PMID: 26014292
PMCID: PMC4534526
Record Identifier: 991031578070702976