Dexrazoxane provides long-term protection against against doxorubicin-induced heart damage in survivors of childhood high-risk acute lymphoblastic leukemia (ALL) and does not compromise oncologic efficacy, a new multicenter study indicates.
Dexrazoxane is approved by the US Food and Drug Administration to treat cardiomyopathy caused by doxorubicin and has been shown to reduce heart damage during doxorubicin treatment in children with ALL. In the current study, published online September 16 in The Lancet Oncology, Steven E. Lipshultz, MD, and his colleagues with the Dana-Farber Cancer Institute Childhood ALL Consortium evaluated the long-term effects of dexrazoxane in survivors of childhood ALL.
Between 1996 and 2000, 100 children with high-risk ALL were randomized to receive doxorubicin (10 doses of 30 mg/m2) and 105 to the same dose of doxorubicin preceded by dexrazoxane (300 mg/m2). After treatment, the researchers obtained echocardiographic measurements of left ventricular (LV) structure and function in survivors and compared them with age-appropriate predicted measurements in healthy children.
Five years after completion of doxorubicin therapy, ALL survivors treated with doxorubicin alone had deficits in several measures of LV functioning compared with healthy children. Scores in ALL survivors who received doxorubicin plus dexrazoxane, however, were not significantly different from those in health children. Subgroup analysis showed that dexrazoxane had a protective effect in girls but not boys, possibly because the study was too small to show small differences in protective effects.
At a median 8.7 years of follow up, event-free survival was similar in the two groups—77% in children treated with doxorubicin alone and 76% in those who received doxorubicin plus dexrazoxane, indicating that dexrazoxane did not reduce the efficacy of doxorubicin therapy.