DIFFERENCES IN DOSE SCHEDULING AS A FACTOR IN THE ETIOLOGY OF ANTHRACYCLINE-INDUCED CARDIOTOXICITY IN EWING SARCOMA PATIENTS

Clinical observation suggested a high prevelance of cardiac morbidity and mortality in children with Ewing sarcoma (ES) treated at B.C's Chi ldren's Hospital. We therefore compared 30 patients treated for Ewing sarcoma between 1978 and 1991 with 26 soft tissue sarcoma (STS) patien ts treated with similar chemotherapy over the same period of time. All patients were evaluated for cardiac function using echocardiography. Shortening fraction (SF) and left ventricular mass index (Massl) were compared before and after treatment. The role of chest irradiation, do se concentration (DG) of adriamycin (AD), total mean doses of AD, cycl ophosphamide (CY) and actinomycin (AC) were analysed. SF for patients with ES and STS postchemotherapy was significantly lower (P much less than .001) and P = 0.0004, respectively) than pretreatment values. Pos tchemotherapy SF for ES was lower than STS (P = 0.0097). Massl for eac h group did not change significantly. Six of the ES patients had postc hemotherapy SF of <0.20, with three in congestive failure, two cardiac deaths and one heart transplant. One additional ES patient had sick s inus syndrome and needed a pacemaker. Among the STS patients only one had SF < .20 and none were symptomatic. There were no significant diff erences in the mean AD, CY and AC doses for ES versus STS. The differe nce in the DC of AD for ES (mean 744) compared to STS (mean = 362) was significant (P = <0.017). Chest irradiation did not appear to increas e the likelihood of cardiotoxicity. ES patients had a higher prevalenc e of cardiac dysfunction compared to STS. Studies are required to eval uate the importance of the components of DC, i.e., size of the individ ual dose and frequency of administration of AD, and to look at other p ossible factors in the causation of cardiomyopathy in ES. (C) 1997 Wil ey-Liss, Inc.