Combined Mitoxantrone Plus Doxorubicin in the Treatment of Breast Cancer

Twenty-three patients with advanced breast cancer were treated with the combination of mitoxantrone and doxorubicin. This study was conducted since there is incomplete cross-resistance between the two drugs, and since data in vitro suggested that mitoxantrone might decrease the cardiotoxicity of concurrently administered doxorubicin by decreasing doxorubicin-induced membrane lipid peroxidation. Of 20 patients who were evaluable for response, 10 (50%) responded. Myelosuppression was pronounced with mitoxantrone doses ranging from 6 to 10 mg/m2 and doxorubicin doses ranging from 30 to 50 mg/m2, but granulocytopenia-related infections were uncommon. Three of 14 patients who had repeated gated cardiac radionuclide scans had reductions in their ejection fractions of 26% or more at relatively small total cumulative doses of the drugs; one patient developed reversible congestive heart failure after having received high cumulative doses of the two drugs. Preliminary clinical data suggest that mitoxantrone does not protect patients from doxorubicin-induced cardiotoxicity. Other toxicity was generally mild.