August 18, 2015 | by Robin Rauzi
It's a reasonable question: Why is the National Cancer Institute funding a study on preventing heart failure?
The answer is reasonable as well: Rates of heart failure are drastically high among childhood cancer survivors — 15 times higher than among people the same age who were never treated for cancer. The biggest culprit appears to be a group of chemotherapy drugs called anthracyclines, which are used to treat up to 60 percent of childhood cancer patients.
Anthracyclines have been linked to cardiomyopathy, a deterioration in the heart muscle. And research by City of Hope assistant professor Saro Armenian, D.O., M.P.H., and others has found that as the cumulative dose goes up, so does the prevalence of heart failure.
Now, Armenian — with a $3.2 million grant from the NCI — is going to assess whether medical intervention might curb that risk.
“Anthracyclines cause heart problems no matter what the age of the patient, and there are already caps on how much you can give someone. But children, from what we can tell, are more susceptible. These drugs destroy the heart cells, and if you do that to a developing heart, the injury is going to be more significant,” Armenian said.
In addition to holding joint appointments in the departments of Pediatrics and Population Sciences, Armenian is also director of City of Hope’s Childhood Cancer Survivorship Program.
The NCI-funded clinical trial will investigate whether the beta-blocker drug carvedilol can halt, or possibly even reverse, damage to the heart muscle in those treated with high-dose anthracyclines.
Beta blockers decrease the frequency and intensity of heart contractions, making it more efficient at pumping blood. But the drugs are usually prescribed only to people with overt heart problems, such as symptomatic heart failure. In this case, Armenian is wondering if carvedilol, at low doses, can work as a prophylactic measure to help prevent the onset of heart failure in cancer survivors at highest risk.
Armenian’s study had been underway for a few years at City of Hope and two other institutions. The recently awarded grant from the NCI will enable the research team to open the study within the Children’s Oncology Group – a cooperative group that coordinates clinical trials across more than 200 hospitals, universities and cancer centers in North America. To enroll in the trial, individuals must be 16 or older and have completed cancer therapy at least two years earlier.
The 250 randomized participants will receive either a two-year course of carvedilol or a placebo. Using echocardiograms and other tests, the investigators will assess whether the drug measurably alters the heart function, or affects blood test results that are indicators of heart health. Researchers will analyze outcomes for subgroups as well, such as those who had very high doses of chemotherapy and radiation, those who were younger at the time of cancer treatment or those who were treated for cancer more than 10 years earlier.
“We know that there is a long latency between the cancer treatment and when therapy-related heart failure develops,” Armenian said. “What we don’t know is the optimal timing for intervention, and whether certain groups of survivors will benefit more than others.”
The NCI grant demonstrates how the frontier of childhood cancer survivorship research is shifting. During the past two decades, a tremendous amount of effort has gone into identifying long-term complications from cancer therapy.
“We’re really moving from the observation stage — describing who is at high risk — to the active stage,” Armenian said. “It is our responsibility as researchers and clinicians to challenge established paradigms of survivorship research, to think about strategies to prevent chronic disease and to give each survivor the opportunity to thrive long after their cancer treatment has been completed.”
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