Dexrazoxane attenuates doxorubicin-associated cardiotoxicity in children

In children with acute lymphoblastic leukemia (ALL), pretreatment with dexrazoxane, a free-radical scavenger, curbs doxorubicin-associated cardiotoxicity without compromising the antileukemic effects of the drug, findings indicate.

“In long-term survivors of childhood ALL, doxorubicin-associated cardiotoxic effects are pervasive, persistent, and often progressive,” investigators explain in the July 8th issue of The New England Journal of Medicine. Dexrazoxane has been shown to protect the heart in adults receiving anthracycline therapy.In a multicenter controlled trial of 206 children with newly diagnosed ALL, investigators randomly assigned 101 to standard-dose doxorubicin alone and 105 to dexrazoxane (300 mg per square meter) immediately before doxorubicin therapy.”Dexrazoxane therapy was associated with a large and statistically significant reduction in heart damage,” study chief Dr. Steven E. Lipshultz from the University of Miami told Reuters Health.Any elevation in troponin T, a sensitive and specific marker of myocardial injury, occurred in 50% of children receiving doxorubicin alone compared with 21% receiving dexrazoxane before doxorubicin (p < 0.001). Moreover, 32% of children in the doxorubicin only arm had "extremely elevated" troponin T levels compared with just 10% of children pretreated with dexrazoxane (p < 0.001).Importantly, Dr. Lipshultz said, dexrazoxane pretreatment "had no impact on the effectiveness of the chemotherapy in the short-term," but he emphasized that longer follow up is needed to "determine the influence of dexrazoxane on survival and heart function." The median follow up in this study was 2.7 years and the event-free survival rate at 2.5 years was similar in both groups (83%).Currently, the optimal dose of dexrazoxane in children is unknown.In an editorial, Drs. Leontine C. M. Kremer and Huib N. Caron of the University of Amsterdam say this study is "an important step toward effective cardioprotection" in children undergoing doxorubicin therapy, adding that there is an "urgent need to prevent" such effects.(Source: N Engl J Med 2004;351:121-123,145-153: Reuters Health: Megan Rauscher: Oncolink: July 2004)