Anthracycline chemotherapy with doxorubicin—a popular and effective treatment choice for pediatric cancer—is associated with an increased incidence of late cardiomyopathy in the pediatric population. Steven Lipshultz and colleagues report promising results from a trial investigating a potentially cardioprotective adjunct to doxorubicin chemotherapy in children with high-risk acute lymphoblastic leukemia (ALL).

“Finding ways to administer anthracyclines to maintain oncologic efficacy while reducing cardiotoxicity is essential,” explains Lipshultz. His team investigated the effects of adding dexrazoxane, an iron chelator, to doxorubicin. 205 patients with high-risk ALL (aged <18 years) were assigned to receive 10 doses of doxorubicin (30 mg/m2 per dose), 105 of whom also received 300 mg/m2 of dexrazoxane before each dose of anthracycline was administered. Echocardiography was used to assess cardiac structure and function 5 years after treatment was completed.

Long-term cardioprotection was observed in the patients receiving dexrazoxane. “We found significantly less left ventricular remodeling, a pathologic process with an ominous prognosis, in the children who received dexrazoxane,” comments Lipshultz. “They also had better left ventricular function and less left ventricular dilation and more normal amounts of heart muscle remaining,” he adds. These beneficial effects were greater in girls than in boys. Dexrazoxane did not reduce the efficacy of doxorubicin; event-free survival at a median follow up of 8.7 years was 77% in the doxorubicin-alone arm and 76% in the doxorubicin plus dexrazoxane arm.

“We recommend that all children newly diagnosed with high-risk ALL who will be receiving anthracycline therapy receive dexrazoxane before each anthracycline dose,” Lipshultz concludes.