The efficacy and toxicity of dexrazoxane use in children with cancer: A population-based study from Maritimes, Canada

Abstract

Anthracycline induced cardiotoxicity is a well-recognized complication in pediatric oncology. The use of the cardio-protective drug dexrazoxane has gained traction despite its unclear efficacy and toxicity. A retrospective, population-based study was completed using chart and database information on children treated with anthracycline at the IWK Health Centre from 2009-2015 (n=178). The efficacy of dexrazoxane was defined as a lack of undesirable deviations in identified cardiac parameters on echocardiogram. Toxicity of dexrazoxane was defined as chemotherapy delays from any of decreased absolute neutrophil count (ANC), decreased platelets, increase in viral/bacterial episodes and febrile neutropenia (FN) episodes. Patients were stratified into groups based on the total amount of anthracycline received and whether they received dexrazoxane. Regardless of anthracycline dose, we found no significant relationships regarding cardiac function in the untreated and dexrazoxane treated groups. However, we found that patients who were treated with >250mg/m2 of anthracycline and received dexrazoxane experienced significantly more platelet delays but no cardiac benefit (p=0.007). When classified by diagnosis, we also found that dexrazoxane treated patients diagnosed with low-risk acute lymphocytic leukemia (LR-ALL) were likely to experience a delay in treatment due to both low ANC (p=0.0001) and the development of FN (p=0.02) whereas high-risk acute lymphocytic leukemia (HR-ALL) patients were likely to experience treatment delays due to thrombocytopenia (p=0.03), low ANC (p=0.0001) and FN (p=0.0001). Despite finding no significant differences regarding the efficacy of dexrazoxane as a cardio-protectant, we have shown that its use induces non-cardiac toxicities in children with cancer that contribute to treatment delays.