TOPLINE

Dexrazoxane was associated with preserved left ventricular (LV) systolic function in childhood cancer survivors treated with doxorubicin in a new analysis. Among 895 patients, those receiving dexrazoxane showed better LV fractional shortening and reduced incidence of LV dysfunction, particularly in high-risk groups where rates approached those of moderate-risk patients.

METHODOLOGY

• The risk for clinical heart failure may exceed 10% by age 50 in childhood cancer survivors exposed to anthracyclines, including doxorubicin, and chest radiation. Dexrazoxane has been associated with reduced adverse LV remodeling shortly after doxorubicin treatment and preserved LV function in long-term childhood cancer survivors, though conclusions may be limited by sample size in previous studies.
• Researchers analyzed echocardiographic data from 895 patients enrolled in Children’s Oncology Group protocols P9404, P9425, P9426, P9754, and Dana-Farber Cancer Institute protocol 95-01, who received doxorubicin treatment with a median dose of 360 mg/m². Participants were followed for a mean of 5.9 years, with 230 patients having a ≥ 10-year follow-up; most protocols featured up-front 1:1 random assignment with dexrazoxane administered as an intravenous bolus before doxorubicin at a 10:1 mg/m² dexrazoxane:doxorubicin dose ratio.
• A total of 2279 evaluable echocardiograms were obtained (1581 centrally remeasured; 698 from institutional reports only), classified as occurring before, during, or after treatment, with a focus on pre- and posttreatment measurements across time periods of < 2, 2-4, 5-9, and ≥ 10 years following treatment completion. 
• Analysis utilized multivariable generalized estimating equations with robust standard errors and Cox proportional hazards models, adjusting for age at cancer diagnosis, age at each echocardiogram, sex, cumulative doxorubicin dose (< 250 vs ≥ 250 mg/m²), chest radiotherapy (yes/no), and echocardiographic data type (centrally measured vs institutional report).
• Patients were categorized as moderate risk (doxorubicin < 100 mg/m² and chest radiation 15-29 Gy; doxorubicin 100-249 mg/m² and chest radiation < 15 Gy) or high risk (doxorubicin 100-249 mg/m² and chest radiation ≥ 15 Gy; doxorubicin ≥ 250 mg/m² regardless of chest radiation), with incidence rates of reduced LV systolic function examined by risk category and dexrazoxane status. 

TAKEAWAY

• Patients treated with dexrazoxane demonstrated preserved LV systolic function with a z-score difference of 0.4 compared with those who did not receive dexrazoxane, with significant differences starting 2-4 years posttreatment (z-score difference, 0.7) and maintained through ≥ 10 years (z-score difference, 0.4).
• Dexrazoxane was associated with decreased hazards of reduced LV function (fractional shortening < 30% or ejection fraction < 50%) occurring after 1 year (hazard ratio [HR], 0.58; P < .05) and 5 years (HR, 0.54; P < .05) postdiagnosis. 
• Among patients classified as high risk per current cardiomyopathy screening guidelines, those assigned to receive dexrazoxane had a lower incidence rate of subsequent reduced LV systolic function (21.8 events/1000 person-years) than those who were not assigned to receive dexrazoxane (40.0 events/1000 person-years; P = .001).
• The protective association between dexrazoxane and more preserved LV fractional shortening and LV ejection fraction values was stronger among women than men and among patients treated with high cumulative doxorubicin doses (≥ 250 mg/m²) than among those exposed to lower cumulative doxorubicin doses. 

IN PRACTICE

“Dexrazoxane exerts a significant doxorubicin cardioprotective effect on LV systolic function long-term and may reduce screening needs,” wrote the authors of the study.

SOURCE

This study was led by Erin M. Mobley, PhD, MPH, of the University of Florida in Jacksonville, and Steven E. Lipshultz, MD, of the University at Buffalo in Buffalo, New York. It was published online on August 6 in the Journal of Clinical Oncology.

LIMITATIONS

Generalizability of the findings could be limited as the study sample reflects a population treated primarily in the late 1990s, and patients with longer follow-up were disproportionately more likely to be non-Hispanic White. Missing clinical data associated with each echocardiogram may limit interpretation, as researchers did not have information regarding whether echocardiograms were obtained while patients were acutely ill for noncardiac reasons or on medications which may affect interpretation of LV systolic function measurements. The study only examined childhood cancer survivors who received doxorubicin, while other types of anthracyclines are also associated with cardiotoxicity. According to the authors, most study patients were still young adults for whom the trajectory of anthracycline-associated changes is largely unknown for patients aging into their fifth or sixth decade of life.

DISCLOSURES

This study received support from the National Institutes of Health (PO1CA068484, RO1CA211996, U10CA098543, U10CA180886, U10CA095861, and UG1CA189955), the St. Baldrick’s Foundation, the Leukemia & Lymphoma Society (6243-13), the Rally Foundation, Sofia’s Hope, Inc., and the Unravel Pediatric Cancer Foundation. Steven D. Colan, MD, disclosed receiving research funding from Rocket Pharma and holding stock and other ownership interests in Rocket Pharma. Richard Aplenc, MD, PhD, disclosed receiving honoraria from Syndax. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.