Differences in dose scheduling as a factor in the etiology of anthracycline-induced cardiotoxicity in Ewing sarcoma patients.

Abstract

Clinical observation suggested a high prevalence of cardiac morbidity and mortality in children with Ewing sarcoma (ES) treated at B.C.'s Children's Hospital. We therefore compared 30 patients treated for Ewing sarcoma between 1978 and 1991 with 26 soft tissue sarcoma (STS) patients 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, dose concentration (DC) of adriamycin (AD), total mean doses of AD, cyclophosphamide (CY) and actinomycin (AC) were analysed. SF for patients with ES and STS postchemotherapy was significantly lower (P < .001 and P = 0.0004, respectively) than pretreatment values. Postchemotherapy SF for ES was lower than STS (P = 0.0097). Massl for each group did not change significantly. Six of the ES patients had postchemotherapy SF of < 0.20, with three in congestive failure, two cardiac deaths and one heart transplant. One additional ES patient had sick sinus syndrome and needed a pacemaker. Among the STS patients only one had SF < .20 and none were symptomatic. There were no significant differences in the mean AD, CY and AC doses for ES versus STS. The difference in the DC of AD for ES (mean 744) compared to STS (mean = 362) was significant (P = < 0.001). Regression analysis indicated a trend for decreasing SF with increasing DC (P = 0.017). Chest irradiation did not appear to increase the likelihood of cardiotoxicity. ES patients had a higher prevalence of cardiac dysfunction compared to STS. Studies are required to evaluate the importance of the components of DC, i.e., size of the individual dose and frequency of administration of AD, and to look at other possible factors in the causation of cardiomyopathy in ES.