Drug Offers Long-Term Heart Protection for Childhood Cancer Survivors

While chemotherapy agents can be toxic to patients’ heart function, recent research showed that children with cancer who were administered dexrazoxane before the chemotherapy agent doxorubicin had fewer cardiac complications for nearly two decades after treatment, compared to those who did not receive dexrazoxane.

These findings come from long-term research that started in the 1990s.

“We were shocked at how effective the dexrazoxane was even five years later, at having pretty much normal heart structure and function. In comparison, those that didn't get it had progressive worsening of their heart function over those five years after having been exposed,” study author Dr. Steven E. Lipshultz, a pediatric cardiologist at Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Oishei Children's Hospital, said in an interview with CURE®.

Doxorubicin is an anthracycline-based chemotherapy that is highly effective and very common in the treatment of childhood cancer. Long after their cancer treatment ended, many survivors would face complications such as congestive heart failure (which is fatal in some cases) or need a heart transplant.

Initial research conducted years ago showed that in children with cancer who were being treated with doxorubicin, those who received dexrazoxane before their treatment tended to have a lower percentage of dead and dying heart tissue than those who did not receive the cardio-protective drug. As such, patients were also able to tolerate higher doses of the chemotherapy drug with fewer concerns about the toxic effects it could have on the heart.

Dexrazoxane is an injection that is used to prevent or decrease the thickening of the heart walls, which can occur after the heart is damaged. Lipshultz explained that when heart muscle dies, it does not regrow back as muscle, but as scar tissue. Too much scar tissue can cause a heart attack (myocardial infarction).

“Our real endpoint(s were) many years later, where the hearts healthier? Were they not symptomatic from heart failure or other heart issues? Could their quality of life be enhanced and maximized? That's what's really most important,” Lipshultz said.

Now, the most recent research, which was published in the Journal of Clinical Oncology, showed that among 195 children with acute lymphoblastic leukemia, Hodgkin lymphoma or osteosarcoma who were treated with doxorubicin between 2 and 18 years ago, those who had dexrazoxane had: superior left ventricular fractional shortening and ejection fraction (which measures how effectively your heart pumps blood) as well as lower myocardial stress, “because 10 or 20 years ago, they lost less heart muscle … now, years later, their heart doesn’t have to work as hard” Lipshultz explained.

“(Childhood cancer survivors) look forward to decades of active and productive life,” Lipshultz said. “If you're sitting there with heart dysfunction, your ejection fractions are reduced or (you have) more stress, so your heart has to work twice as hard to pump the blood out. You get tired and your heart gets tired and your heart wears out sooner. So that's why, to me, (these findings are) really extraordinary. This is the longest follow up ever done for any cardio protectant drug for children, whether they have cancer or not. The fact that it's a lasting long-term improvement, really suggests great things.”

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