Dr. Eric Chow receives three grants for research designed to improve health of childhood cancer survivors

Fred Hutch clinical researcher, epidemiologist and pediatric oncologist Dr. Eric Chow has received three new grants to help him continue research aimed at bettering the lives of childhood and adolescent cancer survivors.

In March, the National Cancer Institute approved a $3.7 million, five-year grant extending Chow’s research into improving treatment of cardiovascular risk factors in childhood cancer survivors. The NCI also awarded Chow a $2.7 million grant to extend, by four years, his research into determining the long-term efficacy of a drug to minimize or prevent heart injury in pediatric cancer patients.

Chow said the two NCI studies are designed to lessen the risk of heart disease later in life for those who were treated as children or adolescents. According to the National Institutes of Health, premature cardiovascular disease is the leading non-cancer cause of death in these survivors.

“We know these survivors have a higher risk as adults because of their treatment as children,” Chow said. “And this risk is probably under-recognized by both the survivors themselves and their primary care physicians.”

Doctors may not think of childhood cancer survivors as being susceptible to heart problems due to their young age, he said, but risk factors like high blood pressure, high cholesterol and diabetes are often more common in these patients compared with peers of the same age who’ve never had cancer.

“There’s a sense that people may not take these conditions as seriously as often they don’t cause symptoms,” he said. “There may also be a hesitancy to treat people for these problems when they’re so young.”

The new grant will fund research that will hopefully “move the needle as far as people having better control over these potentially modifiable conditions that we think will decrease the risk of heart problems later on.”

Chow and his team will apply a risk-prediction algorithm to the 24,500-plus Childhood Cancer Survivor Study cohort to suss out 800 survivors who are most at risk for serious heart disease (Fred Hutch is the Statistical Center for the CCSS). They will then monitor the survivors for high blood pressure, cholesterol issues and diabetes, via at-home visits and the patients’ medical records. Those who are found to be underdiagnosed or undertreated will be eligible to participate in a year-long, randomized, controlled trial designed to improve control of these cardiovascular-disease risk factors through better care coordination with the survivors’ primary-care providers (the control arm will receive the intervention on a delayed basis).

“We can’t undo their chest radiation or the chemotherapy exposure which affected their heart function,” he said. “But there’s good evidence in the general population that high blood pressure or diabetes further increases your risk. So if we can better control those things, maybe we can reduce overall heart-disease risk in these long-term survivors.”

The other NCI grant will investigate whether a cardioprotectant known as dexrazoxane might be useful in curbing cardiomyopathy or heart failure brought on by a common class of chemotherapy drugs known as anthracyclines.

Chow said anthracyclines and related drugs are well-documented as the single most important risk factor associated with subsequent development of cardiomyopathy and heart failure among cancer survivors. The American Society of Clinical Oncology currently recommends dexrazoxane for all adults exposed to high doses of anthracyclines. Safety concerns have limited its use in children, however.

“Dexrazoxane is given at the time of cancer treatment as a primary prevention strategy,” Chow explained. “It’s to prevent subsequent treatment-related heart failure.”

Chow and co-principal investigator Dr. Steven Lipshultz, a pediatric cardiologist based at Wayne State University, will plumb data from a series of clinical trials conducted on 1,200 children with leukemia and lymphoma between 1995 and 2001 in which half of the children were randomly assigned to receive the cardioprotectant with their chemo and half were not. Initial three- to five-year follow-up data suggest that the children who were given dexrazoxane had less heart damage. Chow and his team will look at the heart health of 200 of these childhood cancer survivors, now 15 to 20 years older, and provide longer-term follow-up data on the effectiveness of dexrazoxane as a potential cardioprotectant for children.

“This is basically a test to determine the effectiveness of it as a primary heart-disease strategy,” Chow said. “If dexrazoxane is found to be effective in minimizing or preventing heart injury among these childhood cancer survivors 15 to 20 years after cancer diagnosis, this would have significant implications on current clinical practice and potentially drug regulatory policy.”

Chow’s third grant is a $100,000 award from the Rally Foundation to look at echocardiographic change in cancer survivors at risk for cardiomyopathy. This project will involve cardiologists and oncologists from Seattle Children’s and Fred Hutch as well as City of Hope, Emory University, Hospital for Sick Children in Toronto and the University of Minnesota.

 “We are very excited and grateful for this second year of funding from the Rally Foundation,” Chow said. “This will help us carry our momentum from the first year, where we have been working with four other Children’s Oncology Group sites across the country to learn more about this complication of otherwise successful cancer treatment.”