Longitudinal Change in Cardiac Function After Doxorubicin and Dexrazoxane: A Report From Children's Oncology Group ALTE11C2.

Authors

Erin M Mobley, David R Doody, Steven D Colan, Sanjeev Aggarwal, Richard Aplenc, Saro H Armenian, K Scott Baker, Smita Bhatia, Louis S Constine, David R Freyer, Lisa M Kopp, Wendy M Leisenring, Nao Sasaki, Lynda M Vrooman, Barbara L Asselin, Cindy L Schwartz, Eric J Chow, Steven E Lipshultz

Published in

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. Pages JCO2600260. Aug 06, 2026. Epub Aug 06, 2026.

Abstract

Dexrazoxane has been associated with preservation of left ventricular (LV) systolic function in relatively small studies of long-term childhood cancer survivors. What remains less clear is whether this association is also seen in larger populations over time and what effect dexrazoxane has on cardiomyopathy screening recommendations.
We analyzed echocardiographic data from participants who received doxorubicin treatment and were enrolled on Children's Oncology Group protocols P9404, P9425, P9426, P9754, and Dana Farber Cancer Institute protocol 95-01. Except for P9754, all protocols featured up-front 1:1 random assignment with dexrazoxane administered uniformly as an intravenous bolus before doxorubicin (10:1 mg/m² dexrazoxane:doxorubicin dose). Blinded central echocardiogram remeasurements were used when possible; otherwise, data were abstracted from institutional reports. Differences and associations by ± dexrazoxane were estimated using generalized estimating equations and Cox proportional hazard models, adjusting for age, sex, doxorubicin dose, chest radiotherapy, and echocardiogram data type.
Among 895 patients (mean follow-up, 5.9 years, 230 with ≥10-year follow-up; median doxorubicin dose, 360 mg/m²; 51% dexrazoxane-exposed) with evaluable echocardiograms (n = 2,279; 1,581 centrally remeasured; 698 report only), preserved LV systolic function was observed in patients treated with dexrazoxane (z-score difference 0.4 [95% CI, 0.2 to 0.5]) versus without. Dexrazoxane was also associated with decreased hazards of reduced LV function (fractional shortening <30% or ejection fraction <50%) occurring after 1 (0.58 [95% CI, 0.41 to 0.82]) and 5 years (0.54 [95% CI, 0.31 to 0.93]) postdiagnosis. Finally, dexrazoxane appeared to decrease the incidence of reduced LV function among those classified by current cardiomyopathy screening guidelines as high risk to rates like a lower-risk group (from 40 to 21.8 events/1,000 person-years; P = .001).
Dexrazoxane exerts a significant doxorubicin cardioprotective effect on LV systolic function long term and may reduce screening needs.

PMID:
42561216
Bibliographic data and abstract were imported from PubMed on 07 Aug 2026.

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