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Can Dexrazoxane Provide Cardioprotection During Treatment for Pediatric AML?

Published on June 10, 2020 in Cornerstone Blog · Last updated 3 months 2 weeks ago


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New study shows dexrazoxane lowers risk for cardiotoxicity associated with chemotherapy in pediatric AML.

The findings:

In a study of more than 1,000 pediatric patients with acute myeloid leukemia (AML), researchers found that pre-treatment with dexrazoxane before each round of anthracycline chemotherapy helped mitigate cardiotoxicity often associated with the treatment. Dexrazoxane also was linked to lower treatment-related mortality, and it did not increase other non-cardiac toxicities.

Why it matters:

Curative therapy for pediatric AML involves high doses of anthracycline chemotherapy. Although this treatment is highly effective at killing cancer cells, it is also highly cardiotoxic. Historically, only 5% to 10% of patients receive dexrazoxane to prevent cardiotoxicity, which in light of the study findings underscores the potential impact that may be realized, should it become standard of care.

Who conducted the study:

Richard Aplenc, MD, PhD, MSCE, led the Children’s Oncology Group (COG) study. Dr. Aplenc is assistant vice president and chief clinical research officer at CHOP, professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania, and core faculty member of the Clinical Futures, a CHOP Research Institute Center of Emphasis. The first author was Kelly D. Getz, PhD, MPH, also a core faculty member of the Clinical Futures, and assistant professor of Epidemiology at the Perelman School of Medicine at the University of Pennsylvania.

How they did it:

The multicenter study included 1,014 patients with AML treated on the COG trial AAML1031 between 2011 and 2016. Treating physicians chose whether to administer dexrazoxane: 96 patients consistently received dexrazoxane with each round of anthracycline chemotherapy, and the remaining patients never received dexrazoxane. After each course of treatment, and at regular intervals during follow-up, the researchers measured ejection fraction and shortening fraction to determine cardiac dysfunction.

Patients who received dexrazoxane had a significantly lower risk for left ventricular systolic dysfunction than patients who did not (26.5% vs. 42.2%). Patients in both groups had similar 5-year event-free survival and overall survival rates without increasing noncardiac chemotherapy toxicity, and the results suggest a lower treatment-related mortality among patients who received dexrazoxane (5.7% vs. 12.7%).

Quick thoughts:

“We demonstrated the benefit of dexrazoxane with respect to the cardioprotection and secondarily, the suggestion of a lower treatment-related mortality,” Dr. Getz said. “These findings are practice-changing: The upcoming COG Phase III clinical trial for AML will include a requirement to administer dexrazoxane for cardioprotection to patients receiving standard anthracycline chemotherapy.”

What’s next:

“While dexrazoxane was shown to be very effective, it didn’t provide complete protection against declines in cardiac function,” Dr. Getz said. “Therefore, some of the additional work we are focusing on is finding additional cardioprotective treatment strategies, and identifying subpopulations who would achieve the greatest benefit from the different approaches to prevention. In addition, we’re exploring appropriate cardiac monitoring schedules: What is the appropriate timing of cardiac monitoring for those on treatment, and during long-term follow-up?”

Where the study was published:

The study appeared in the Journal of Clinical Oncology.

Where to learn more:

Read more about the study in a CHOP press release.