Clinical status and optimal use of the cardioprotectant, dexrazoxane

Anthracycline antibiotic use is limited by cardiac toxicity. The risk factors are cumulative dose, radiation to the chest and mediastinum, age, and preexisting myocardial impairment. Dexrazoxane (Zinecard) can prevent anthracycline cardiac toxicity by intracellular chelation of iron. In a phase III placebo-controlled trial, women with breast cancer were treated with a doxorubicin-based three-drug regimen. Half the women also received dexrazoxane, while half did not. In an intent-to-treat analysis, 76 patients were randomized to the experimental group and 74 to the control group. Cardiac toxicity occurred in 34% of women in the control group, as compared with 7% of the experimental group. The median dose of doxorubicin was 440 mg/m² in the control group (range, 25 to 850 mg/m²) vs 500 mg/m² in the experimental group (range, 50 to 2,150 mg/m²). Dexrazoxane-treated patients had similar response rates and toxicities as the control group. Cardioprotection is also evident if dexrazoxane is not initiated until a 300- mg/m² cumulative dose of doxorubicin is reached. In summary, the clinician should consider dexrazoxane when assessing the potential clinical benefit of doxorubicin therapy in patients with an increased risk of cardiac toxicity.