Results of randomized study on dexrazoxane administration in children with de novo acute leukemia

Abstract

9037 Background: Anthracyclins and anthracenediones represent major drugs for both AML and ALL. Among other mechanisms, these drugs induce free radical production responsible of cardiac toxicity. It appeared very important to protect cardiomyocytes. Dexrazoxane (DZ) was developed in this goal. In adult patients, its efficiency was demonstrated both to protect heart and to respect anticancer therapy. We conducted a prospective single bind randomized study using DZ in pediatric acute leukemia. Methods: From Dec 00 to Sept 03, 16 patients (pts) were enrolled for receiving or not DZ (1g for 50mg of doxorubicin equivalent dose) with chemotherapy. Cardiac function was evaluated by echocardiogram before induction and after each chemotherapy course of either EORTC 58951 (arm VHR) or LAME01 trials and each year after treatment completion. The cardiologist operator did not know if child received DZ or not. The cumulative equivalent doxorubicin doses were 310 and 450mg/m2 for EORTC 58951 and LAME01, respectively. The primary end-point was cardiac function evolution. The secondary end points were OS, EFS and the respect of therapy schedule. Results: 16 pts (9M/7F, 11AML/5ALL), median age 8.5y (2.4 - 16.1) were enrolled. 5 AML and 3 ALL pts received DZ. Median f-up was 28.5 months (10–47). Mean left ventricular shortening fractions were 39 and 35% in pts without DZ and 40 and 39% in pts with DZ before chemotherapy and 1 year after diagnosis, respectively. Mean wall stress values were 50 and 50g/cm2 for patients without DZ and 39 and 38g/cm2 for pts with DZ. All these values were comparable. 12 pts were alive, 6 in each arm. 1 pt relapsed in DZ arm and 3 in the other arm. 2 pts died of disease and 2 from infection equally dispatched in the 2 arms. Mean time between successive chemotherapy courses was identical in different groups. 2 patients given DZ presented severe hepatic toxicity (≥grade 3 of WHO classification) followed by quick and spontaneous regression. None other toxicity > grade 1 were observed. Conclusions: DZ may be used safely in children receiving anthracycline. No difference in OS and DFS appear in our study. Median follow-up was probably too short for distinguishing any cardiac alteration, and patient number was low. No significant financial relationships to disclose.