Researchers discovered that the blood vessel–relaxing agent carvedilol may be safe and effective at reducing the risk of heart failure in childhood cancer survivors, according to a recent study published by Armenian et al in The Lancet Oncology. These findings indicate carvedilol may improve important biomarkers of heart injury caused by exposure to chemotherapy.
Background
One of the severe long-term side effects of the anthracycline class of chemotherapy agents is an increased risk of heart failure. This is a delayed process in which the heart undergoes gradual changes over time characterized by the thinning of the heart muscle and enlargement of its chambers. Once heart function begins to decline, the process is irreversible—highlighting an urgent need for early prevention strategies.
“The growing number of childhood cancer survivors makes the development of early interventions imperative. Just helping [pediatric patients] survive cancer isn’t enough. We also need to optimize [their] health, so they don’t have to face life-threatening side effects decades after they are cancer free,” emphasized lead study author Saro H. Armenian, DO, MPH, the Barron Hilton Chair in Pediatrics at City of Hope Children’s Cancer Center.
Study Methods and Results
In this phase IIb clinical trial, the researchers recruited 182 childhood cancer survivors from 30 Children’s Oncology Group member hospitals across the United States and Canada. The patients were assigned to receive relatively low doses of carvedilol or equivalent placebo for a period of 2 years. The researchers reported there were no statistically significant differences in side effects between the two groups and carvedilol was well tolerated.
Although the researchers did not achieve their goal of decreasing the thinning of the heart muscle and enlargement of its chambers, there were significant improvements in heart left ventricular end-systolic wall stress, an early biomarker of worsening heart health.
Conclusions
“The greatest benefit was seen in [patients] who were very long-term survivors as well as in those who were highly adherent to [carvedilol]. Moreover, of the eight patients who developed clinically significant decline in heart function [during] the study, six were randomized to placebo and two were receiving carvedilol,” Dr. Armenian explained. “Our research sets the stage for a phase III clinical trial that may demonstrate a significant benefit for certain patients who are at an especially high risk of irreversible heart function decline after completion of cancer therapy,” he highlighted.
“Conducting this study across 30 institutions and among long-term survivors of childhood cancer illustrates the strengths of the [Children’s Oncology Group] network. An intervention study on this scale would not be feasible outside of [the Children’s Oncology Group]. Future research will need to focus on the optimal timing, duration, and population for carvedilol intervention,” suggested Douglas S. Hawkins, MD, Professor of Hematology-Oncology at the Seattle Children’s Hospital and Chair of the Children’s Oncology Group.
The researchers concluded that these recent findings may be a critical first step toward developing future studies that will seek to optimize the long-term well-being and health of cancer survivors who are expected to live for decades after their initial cancer diagnosis.
Disclosure: The research in this study was supported by the National Cancer Institute, the National Cancer Institute’s Community Oncology Research Program, St. Baldrick’s Foundation, the Leukemia & Lymphoma Society, the Altschul Foundation, the Rally Foundation, and the American Lebanese Syrian Associated Charities. For full disclosures of the study authors, visit thelancet.com.
