Intensive single-agent mitoxantrone for metastatic breast cancer

Abstract

Twenty-seven women with metastatic breast cancer were treated with mitoxantrone as a single agent, with the use of an intensive dose-escalating schedule. Doses were given at 0.5 mg/m2/day as an iv injection for 3 consecutive days and then were escalated each month by 2.5 mg/m2/day until maximal tolerance was reached on the basis of hematologic or cardiac toxicity. No complete responses were demonstrated. Six patients (22%) had partial responses of 5.5 months' median duration. Four of 12 patients who had not received prior doxorubicin responded (33%), whereas two of 15 patients with previous doxorubicin exposure responded (13%). Cardiotoxicity, determined by serial radionuclide ventriculography, occurred in 10 patients (37%) at a mean total mitoxantrone dose of 83.0 mg/m2. Three of these 10 patients had no predisposing risk factors, four had received thoracic radiotherapy that might have involved the heart, and three had received prior doxorubicin without clinical toxicity. The failure of dose intensification to augment the response rate when compared to the response rates reported for less myelotoxic doses of the drug, in addition to the extent of cardiotoxicity noted, calls into question the value of dose intensification of mitoxantrone in the treatment of metastatic breast cancer.