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Late Mortality After Dexrazoxane Treatment: A Report From the Children's Oncology Group. J Clin Oncol 2015 Aug 20;33(24):2639-45

Date

05/28/2015

Pubmed ID

26014292

Pubmed Central ID

PMC4534526

DOI

10.1200/JCO.2014.59.4473

Scopus ID

2-s2.0-84940502191   38 Citations

Abstract

PURPOSE: 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.

PATIENTS AND METHODS: 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.

RESULTS: 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.

CONCLUSION: Among pediatric patients with leukemia or lymphoma, after extended follow-up, dexrazoxane use did not seem to compromise long-term survival.

Author List

Chow EJ, Asselin BL, Schwartz CL, Doody DR, Leisenring WM, Aggarwal S, Baker KS, Bhatia S, Constine LS, Freyer DR, Lipshultz SE, Armenian SH

Author

Cindy L. Schwartz MD, MPH Chief, Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Antineoplastic Combined Chemotherapy Protocols
Child
Child, Preschool
Dexrazoxane
Doxorubicin
Drug Interactions
Female
Hodgkin Disease
Humans
Infant
Male
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Young Adult
jenkins-FCD Prod-461 7d7c6113fc1a2757d2947d29fae5861c878125ab