Dexrazoxane Preserved Cardiac Function in Children Undergoing Chemotherapy for AML

For pediatric patients undergoing chemotherapy treatment for acute myeloid leukemia (AML), dexrazoxane preserved cardiac function without compromising overall survival and event-free survival or increasing noncardiac toxicities, according to a study published in the Journal of Clinical Oncology.^1-2

The researchers from the Children’s Hospital of Philadelphia (CHOP) believe that dexrazoxane, a cardioprotective drug, could potentially improve the overall patient survival rate and should be considered for cardioprotection during front-line treatment of AML.

“This study provides important evidence that using dexrazoxane helps prevent heart damage in children undergoing treatment for AML,” senior author of the study Richard Aplenc, MD, PhD, said in a press release.² “These results have arguably changed the standard of care for pediatric AML treatment.”

The results showed that patients who received dexrazoxane had significantly smaller ejection fraction and shortening fraction declines, as well as a lower risk for left ventricular systolic dysfunction than unexposed patients across courses (26.5% vs 42.2%; HR, 0.55; 95% CI, 0.36-0.86; P= .009).

More, patients who received dexrazoxane had similar 5-year event-free survival (49.0% vs 45.1%; P= .534) and overall survival rates (65.0% vs 61.9%; P= .613) to those unexposed, but there was a suggestion of lower treatment-related mortality with dexrazoxane-exposed patients (5.7% vs 12.7%; P= .068).

A total of 1,092 patients were examined in this study, with 96 patients exposed to dexrazoxane at anthracycline course, and 918 patients never exposed to the cardioprotective drug. More, 78 patients received dexrazoxane at some points but not all of their treatments. This group was excluded from the final results. The demographic distribution was relatively even between both groups.

“To our knowledge, these data are the first demonstration of a potential survival benefit with dexrazoxane, specifically a reduction in treatment-related mortality,” first author of the study Kelly D. Getz, PhD, MPH, said in a press release. “This suggests that dexrazoxane may directly prevent acute, severe cardiac events that contribute to early deaths. Additional research to understand the underlying biology of anthracycline-associated cardiotoxicity and effective interventions will improve both the cardiovascular and oncologic outcomes for children with cancer.”

Anthracyclines were proven to improve survival rates for pediatric patients with AML, but the drugs came with cardiac side effects. These drugs “generate iron-mediated free radicals and inhibit DNA replication,” which triggers cell death and left ventricular systolic dysfunction while also possessing the possibility to lead to heart failure.

The dexrazoxane interferes with the iron-mediated free radical formation and cell death caused by anthracyclines, helping to mitigate side effects. Even with this information, dexrazoxane is used in less than 5% of pediatric patients with AML in the United States.

References:

1. Getz KD, Sung L, Alonzo TA, et al. Effect of dexrazoxane on left ventricular systolic function and treatment outcomes in patients with acute myeloid leukemia: a report from the Children’s Oncology Group. Journal of Clinical Oncology. DOI: 10.1200/JCO.19.02856.

2. Cardioprotective Drug Prevents Severe Cardiac Events in Children Undergoing Chemotherapy for Acute Myeloid Leukemia [news release]. Philadelphia, Pennsylvania. Published April 28, 2020. https://www.newswise.com/articles/cardioprotective-drug-prevents-severe-cardiac-events-in-children-undergoing-chemotherapy-for-acute-myeloid-leukemia?sc=mwhr&xy=10021790. Accessed May 11, 2020.