About 75 percent of children with leukemia who receive chemotherapy face life-threatening heart problems as they get older, but adding a known cardio-protective drug may prevent the damage. Presented June 4 at the American Society of Clinical Oncology (ASCO) meeting in Chicago, the study evaluated the the effectiveness of the drug Zinecard (dexrazoxane), at protecting the heart during treatment of acute lymphoblastic leukemia. Barbara Asselin, professor of pediatrics and oncology at the University of Rochester Medical Center, presented the data and also took part in a larger forum that discussed heart disease and second malignancies—the unfortunate, severe risks associated with aggressive treatment of children. “Today the majority of children with leukemia will be cured,” Asselin says. “As our young people survive, though, we believe we will see many more cardiac issues. It is a problem that must be fixed because it is the leading cause of death later in life among these patients.” One part of the equation involves getting teenagers and young adult cancer survivors, who tend to engage in riskier behaviors, to be aware of potential problems and make healthy lifestyle choices—no smoking; exercise; and careful follow-up appointments with a physician, Asselin says. Drugs such as Zinecard are also important, although the data so far has been inconsistent. The URMC study evaluated 537 patients for more than 10 years after they were treated for leukemia between 1996 and 2001. All received multi-agent chemotherapy that included doxorubicin, known to be toxic to the heart. Patients were randomized into two groups, with or without a dose of intravenous Zinecard immediately prior to receiving the chemotherapy. Later, researchers assessed each patient for heart damage at three different points after chemotherapy. Using standard measures, they looked at heart muscle function and structure. (A common problem following doxorubicin therapy is heart enlargement and thinning of the ventricular walls.) For both groups of patients, the five-year survival with no evidence of leukemia was the same. That data was encouraging and very important, Asselin says, because of concern in the pediatric community that adding Zinecard to the treatment regimen might interfere with the chemotherapy’s ability to attack the leukemia. In addition, the group that did not receive Zinecard had more episodes of acute heart problems, and researchers saw more damage over time to the heart structure and function, as compared to the group that did receive the cardio-protective drug. Earlier clinical trials of Zinecard in women with breast cancer, who had already received high doses of doxorubicin and needed more chemotherapy, showed that the drug could protect the heart during retreatment. A problem with Zinecard, however, is an increased rate of second malignancies in the children who received the heart drug. Although the higher rate did not reach conventional levels of statistical significance by research standards, it is worth noting and studying further, Asselin says. “We now have some very effective cancer treatments at our disposal. But we really need to focus on promoting the good health of our survivors. Our care does not end with chemotherapy. Being there for many years into the future, and to help childhood survivors understand their risks, is so important.”
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