Association of early dexrazoxane with reduced cardiotoxicity risk in sarcoma patients treated with anthracycline chemotherapy

Abstract

Background Cardiotoxicity is a concern for patients with sarcoma receiving anthracyclines. Dexrazoxane reduces this risk; however, the timing of administration varies in practice. This study evaluated the association between dexrazoxane timing and anthracycline cardiotoxicity risk. Patients and methods This retrospective, single-center cohort study included adults with sarcoma treated with anthracyclines from 2010 to 2020 with a baseline and ≥1 follow-up echocardiogram. “Early” dexrazoxane was defined as starting with the first anthracycline dose; “later” as starting with the second or subsequent doses. The primary endpoint was time to cardiotoxicity (decline in left ventricular ejection fraction [LVEF] ≥10%-<50% from baseline). Associations were evaluated using multivariable Cox proportional hazards models. Results Among 672 patients, the median doxorubicin-equivalent dose was 300mg/m2 (interquartile range [IQR]: 200-444mg/m2); dexrazoxane was administered early in 130 patients (19.3%) and later in 275 (40.9%). Over a median follow-up of 8.6 months (IQR: 3.9-23.1 months), 48 (7.1%) developed cardiotoxicity. Among patients who received a cumulative anthracycline dose >300mg/m2, those receiving early dexrazoxane had an 85% reduction in cardiotoxicity risk (hazard ratio, 0.15; 95% CI, 0.02-0.99) compared to those who did not receive dexrazoxane, adjusting for age, diabetes, and baseline LVEF. Early dexrazoxane was not significantly associated with cardiotoxicity risk among patients who received a cumulative anthracycline dose ≤300mg/m2. Conclusions Early dexrazoxane is significantly associated with lower cardiotoxicity risk in adults with sarcoma receiving anthracycline doses >300mg/m2. These findings support the potential benefit of early dexrazoxane use in patients at elevated risk for anthracycline-induced cardiotoxicity; however, further validation is warranted.