Dexrazoxane: A New Cardioprotective Agent

Abstract

Objective: To review the literature discussing the use of dexrazoxane (e.g., Zinecard, ICRF-187) to prevent doxorubicin-induced cardiotoxicity. Data Sources: Pertinent English-language reports of studies in humans were retrieved from a MEDLINE search (January 1980-January 1997); search terms included chelating agents, razoxane, dexrazoxane, Zinecard, ICRF-187, ADR-529, and ICRF-159. Study Selection: Representative articles discussing the chemistry, pharmacology, pharmacokinetics, dosing, and administration of dexrazoxane and those discussing clinical trials were selected. Data Extraction: Data were extracted and analyzed if the information was relevant and consistent. Studies were selected for review in the text on the basis of study design and clinical end points. Data Synthesis: Dexrazoxane is a chemoprotective agent developed to prevent cardiac tissue toxicity. Dexrazoxane exerts a cardioprotective effect with some clinically significant toxicities; it may also interfere with the antitumor activity of doxorubicin. Until there are sufficient data to support its use in first-line supportive care therapy, dexrazoxane should be reserved for use in patients responding to doxorubicin-based chemotherapy but who have risk factors for cardiac toxicity or have received a cumulative doxorubicin bolus dose of 300 mg/m2. Conclusions: The management of doxorubicin-induced cardiotoxicity has led to the development of supportive care drugs that specifically counteract the dose-limiting toxicities. Dexrazoxane may not completely eliminate the concern about doxorubicin-induced cardiotoxicity, but it may open new avenues for continuing doxorubicin-based chemotherapy.