Protective effects of cardioxane against anthracycline-induced cardiotoxicity in relapsed acute myeloid leukemias

Abstract

The clinical use of anthracyclines and related antitumor agents is limited by their cumulative dose-related cardiac toxicity. Cardioxane (ICRF-187) is an agent that has been recommended to block selectively this toxicity which e.g. limits the use of daunorubicin (DNR) in doses higher than 550-700 mg/m2. We decided to use cardioxane in patients with relapsed acute myeloid leukemias (AML) who have previously been treated with DNR doses above 500 mg/m2. Seven patients with relapsed AML received cardioxane 30 min before DNR or mitozantrone (MTZ) in doses 8-13x higher than DNR or 40-60x higher than MTZ. Two patients received anthracyclines cumulative doses corresponding to more than 1300 mg/m2 and 1000 mg/m2 of DNR, respectively, without any signs of cardiac toxicity. The other 5AML patients in relapse received 1-3 chemotherapy cycles with cardioxane. Their total cumulative doses of DNR were 550-750 mg/m2 and their left ventricular ejection fraction remained above 50% as were their pretreatment values. Cardioxane seems to be a useful cardioprotective agent in relapsed AML which enables further treatment with anthracyclines.