Doctors at City of Hope, one of the largest cancer research and treatment organizations in the United States, have conducted the largest clinical study to date in collaboration with the Children’s Oncology Group (COG) to reduce the risk of heart failure in childhood cancer survivors. The results published in The Lancet Oncology show that the intake of the blood vessel-relaxing drug Carvedilol in childhood cancer survivors is safe and can improve important markers for heart damage resulting from chemotherapy exposure.
A devastating long-term side effect of a class of chemotherapies called Anthracyclines is the increased risk of heart failure, where the heart is unable to pump enough blood to meet the body’s needs. This is a delayed process in which the heart undergoes gradual changes over time, characterized by thinning of the heart muscle and enlargement of its chambers. Unfortunately, the downward cascade following the onset of deterioration in heart function is irreversible, highlighting the urgent need for early prevention strategies.
“The increasing number of childhood cancer survivors makes the development of early interventions imperative. It is not enough to just help children survive cancer. We also need to optimize the health of patients so they are not confronted with life-threatening side effects decades after their cancer-free years.”
Saro H. Armenian, DO, MPH, Barron Hilton Chair in Pediatrics at City of Hope Children’s Cancer Center and corresponding author of The Lancet Oncology study
Doctors at City of Hope led the randomized, double-blind clinical phase 2B trial conducted in 30 COG member hospitals in the United States and Canada (COG study ID: ALTE1621). Approximately 182 enrolled participants took relatively low doses of Carvedilol or an equivalent placebo for two years. There were no significant differences in side effects between the two study arms, and Carvedilol appeared to be well tolerated.
Although the clinical trial did not reach its goal of reducing thinning of the heart muscle and enlargement of its chambers, there were significant improvements in left ventricular postsystolic wall tension of the heart, an early biomarker for worsening heart health.
“The greatest benefit was observed in participants who survived very long periods, as well as in those who strongly adhered to the study medication. Furthermore, six of the eight patients who experienced clinically significant worsening of heart function during the study were randomized to receive a placebo and two received Carvedilol,” said Armenian. “Our research lays the groundwork for a phase 3 clinical trial that could demonstrate substantial benefit for certain patients at high risk of irreversible worsening of heart function after completing cancer therapy.“
Douglas S. Hawkins, MD, chair of the COG group and professor of Hematology-Oncology at Seattle Children’s Hospital, added: “Conducting this study in 30 facilities and among long-term childhood cancer survivors illustrates the strengths of the COG network. An intervention study of this scale would not be feasible outside of COG. Future research should focus on the optimal timing, duration, and population for a Carvedilol intervention.“
This study is an important first step in the development of future studies aimed at optimizing the long-term well-being and health of survivors expected to live decades after their initial cancer diagnosis.
Armenisch, SH, et al. (2024) Wirkung von Carvedilol im Vergleich zu Placebo auf die Herzfunktion bei Anthracyclin-exponierten Überlebenden von Krebs im Kindesalter (PREVENT-HF): eine randomisierte, kontrollierte Phase-2b-Studie. Die Lancet-Onkologie. doi.org/10.1016/S1470-2045(23)00637-X.