Phase II study of mitoxantrone by 14-day continuous infusion with granulocyte colony stimulating factor (GCSF) support in patients with metastatic breast cancer and limited prior therapy

Purpose: Early phase II evaluation of intravenous bolus mitoxantrone indica ted objective response rates of 17-36% in patients with metastatic breast c ancer. Subsequently, it has been suggested that continuous infusion may be the optimal way to administer this drug in order to achieve maximal cytotox ic effect with minimal toxicity. We present the results of a phase II study that evaluated the efficacy and side effects of mitoxantrone administered at the maximally tolerated dose by continuous infusion in patients with met astatic breast cancer. Methods: This study included 16 patients with metast atic breast cancer and limited previous therapy for their metastatic diseas e. Mitoxantrone, 1.5 mg/m(2) per day, was given by continuous intravenous i nfusion for 14 consecutive days repeated every 21 days with. concomitant gr anulocyte colony-stimulating factor support. Dose escalation was allowed. R esults: No complete tumor response was seen. Two patients (13%, CI 0-39%) h ad a partial response, nine patients (56%) had progressive disease and the remaining five patients (31%) had stable disease on therapy. The major dose -limiting side effect was myelotoxicity. Two of the 16 patients (13%) exper ienced asymptomatic cardiotoxicity that required discontinuation of therapy . Conclusions: Our results indicate limited antitumor activity and signific ant toxicity of mitoxantrone given by continuous infusion as second-line ch emotherapy for metastatic breast cancer. The objective response rate docume nted in this study is inferior to response rates reported with other second -line regimens, particularly the taxanes, now available for this patient po pulation.