Dexrazoxane Preserves Cardiac Function in Childhood Cancer Survivors, Suggests Study
USA: Researchers have found in a new analysis of 895 childhood cancer survivors treated with doxorubicin that dexrazoxane was associated with better preservation of left ventricular systolic function. Patients who received dexrazoxane had higher LV fractional shortening and a lower incidence of LV dysfunction, with the greatest benefit seen in high-risk patients, whose outcomes approached those of moderate-risk groups.
The findings, published in the Journal of Clinical Oncology, were reported by Erin M. Mobley, PhD, MPH, Department of Surgery, College of Medicine Jacksonville, University of Florida, Jacksonville, Florida, and colleagues.
Doxorubicin is an important component of treatment for several childhood cancers but can cause cardiac injury that may become apparent years after therapy. Dexrazoxane has been investigated as a cardioprotective agent, although uncertainty has remained about whether its benefits persist over the long term and whether its use could influence recommendations for cardiomyopathy surveillance.
For the study, investigators analyzed echocardiographic data from children treated with doxorubicin who participated in several Children’s Oncology Group protocols and one Dana-Farber Cancer Institute protocol. In most studies, participants were randomly assigned to receive dexrazoxane or no dexrazoxane before doxorubicin. The cardioprotective drug was administered intravenously at a 10:1 dose ratio relative to doxorubicin.
Researchers evaluated 2,279 echocardiograms from 895 patients, including 1,581 examinations that underwent central remeasurement. Participants had a mean follow-up of 5.9 years, while 230 had at least 10 years of follow-up. The median cumulative doxorubicin exposure was 360 mg/m², and 51% of patients had received dexrazoxane.
Key findings included:
- Patients treated with dexrazoxane demonstrated better-preserved LV systolic function, with a 0.4-point higher LV function z-score compared with those who did not receive the drug.
- Dexrazoxane was associated with a lower risk of developing reduced LV function, defined as fractional shortening below 30% or ejection fraction below 50%.
- The hazard of reduced LV function was 42% lower at 1 year after diagnosis and 46% lower at 5 years among dexrazoxane-exposed patients.
- Among patients considered high risk under current cardiomyopathy screening guidelines, the incidence of reduced LV function fell from 40 to 21.8 events per 1,000 person-years with dexrazoxane.
- The reduction in cardiac dysfunction among high-risk survivors brought their observed event rates closer to those seen in lower-risk groups.
The researchers noted that the findings provide evidence of a sustained cardioprotective association between dexrazoxane and cardiac function following childhood cancer treatment. The analysis incorporated adjustments for factors including age, sex, cumulative doxorubicin exposure, chest radiotherapy, and the source of echocardiographic measurements.
The authors concluded that dexrazoxane was linked to sustained preservation of LV systolic function and lower cardiac dysfunction, particularly among high-risk survivors. The findings may eventually inform cardiomyopathy surveillance strategies, although further research is needed before screening recommendations change.
Reference:
Erin M. Mobley et al. Longitudinal Change in Cardiac Function After Doxorubicin and Dexrazoxane: A Report From Children's Oncology Group ALTE11C2. J Clin Oncol 0, JCO-26-00260. DOI:10.1200/JCO-26-00260
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