Phase II trial of a combination of doxorubicin and mitoxantrone in metastatic breast cancer.

To exploit possible different non-cross-resistant mechanisms of cytotoxicity, 25 patients with advanced breast cancer were given combination chemotherapy consisting of iv mitoxantrone (7 mg/m2) and doxorubicin (30 mg/m2) every 3-4 weeks. The patients had predominantly visceral disease and received a median of six (range, one to 12) cycles of therapy. There were no complete responders, but 13 patients (52%) achieved partial remission lasting a median of 8 months (range, 4-21+). Three patients (12%) had disease stabilization and nine (36%) had disease progression. Hematologic toxicity was generally mild, with median wbc count and platelet count nadirs of 1900/mm3 (range, 700-3100) and 160,000/mm3 (range, 49,000-406,000), respectively. One patient may have died from treatment-related sepsis (pneumonia), but lymphangitic lung disease was not excluded. Hair loss progressing to severe alopecia over several treatment cycles was relatively common, affecting seven of 16 evaluable patients (44%). Vomiting was mild or absent in 17 (71%) of 24 evaluable patients. Three of 15 patients in whom serial measurements of left ventricular ejection fraction were performed developed significant reductions compatible with anthracycline-induced cardiotoxicity. Two of these patients also had pericardial effusions and one developed congestive heart failure. In conclusion, mitoxantrone and doxorubicin is an active, well-tolerated drug combination for the treatment of advanced breast cancer but may have appreciable cardiotoxicity.