DOXORUBICIN CARDIOTOXICITY IN CHILDREN - COMPARISON OF A CONSECUTIVE DIVIDED DAILY DOSE ADMINISTRATION SCHEDULE WITH SINGLE-DOSE (RAPID) INFUSION ADMINISTRATION

Background. Doxorubicin cardiotoxicity remains a serious problem in ch ildren with malignancy. The present study was undertaken to determine if the administration of consecutive divided daily doses of doxorubici n would significantly reduce the likelihood of cardiotoxicity in child ren compared with a single dose administration regimen. Procedure. One hundred thirteen children (60 boys and 53 girls) received doxorubicin either by single dose infusion or by a consecutive divided daily dose schedule. The divided dose patients received one third of the total c ycle dose over 20 minutes for 3 consecutive days. Patients treated acc ording to a single dose schedule received the cycle dose as a 20-minut e infusion. The mean doxorubicin dose was 341 mg/m(2). Patients were f ollowed up for 4-180 months. There were 60 boys and 53 girls in the se ries. Results. Fifteen patients developed cardiacdysfunction, eight of whom died of progressive cardiac failure. There was no significant di fference in the incidence of cardiac dysfunction between the divided a nd single dose infusion groups. More girls than boys developed cardiac dysfunction and more girls died of progressive cardiac failure; this difference was not statistically significant. The median time to the d evelopment of cardiac failure was 2 months. Conclusions. The divided d ose regimen did not alter the incidence of cardiotoxicity. Other sched ules should therefore be investigated. Our data suggest that, at simil ar cumulative doses, girls are more likely to develop cardiac dysfunct ion than are boys. If the sex-related difference is proved in larger s eries of patients, it may be prudent to lower the recommended cumulati ve doses for girls. (C) 1998 Wiley-Liss, Inc.