A potent chemotherapy that is highly effective in treating the most common form of childhood leukemia can significantly harm the heart, but findings from a multi-center study led by Dana-Farber Cancer Institute researchers suggest that adding an experimental drug to the therapy can reduce or prevent the damage.
If longer-term studies confirm the results, it would be the first strategy proven to reduce the heart problems that some acute lymphoblastic leukemia (ALL) survivors develop years after being treated with doxorubicin (Adriamycin). The study will be published in the July 8 issue of the New England Journal of Medicine.
“These findings demonstrate that it is possible to decrease some of the chemotherapy’s toxic effects on the heart,” explains Stephen R. Sallan, MD, senior author of the paper and chief of staff at Dana-Farber.
The use of doxorubicin in children with ALL makes it a highly curable disease, but because the chemotherapy kills heart muscle cells as a side effect, survivors can experience an improperly beating left ventricle, congestive heart failure, or arrhythmias that can cause sudden death. One study estimated that, even 25 years after they were treated, their risk of dying from heart disease is more than eight times normal.
More than 200 children under 18 who had newly diagnosed ALL that was considered high-risk – more life threatening than average – between 1996 and 2000 were invited to participate in the multi-center study.
One group (101 participants) was treated with doxorubicin alone – the standard therapy. The other (105 participants) received doxorubicin and dexrazoxane (Zinecard), an experimental drug manufactured by Pfizer, Inc. that has shown to be cardioprotective in adults receiving chemotherapy.
Studies have shown that doxorubicin injures the heart muscle when it is metabolized. As the body breaks down the drug, “free radicals” – chemicals that are toxic to heart cells – are produced. Dexrazoxane, conversely, is “free radical scavenger” that mops up the harmful substances and reduces the muscle damage.
For a preliminary assessment, the scientists compared blood levels of troponin T, a protein that is elevated when the heart had been injured. This test can detect heart damage before it can be seen with echocardiograms.