1. ¹Operative Unit of Medical Oncology, Oncology Institute, Via Amendola 209, Bari, Italy
2. ²Operative Unit of Breast Cancer Surgery, Oncology Institute, Via Amendola 209, Bari, Italy
3. ³Operative Unit of Cardiology, Oncology Institute, Via Amendola 209, Bari, Italy

Correspondence: Dr V Lorusso, E-mail: vitolorusso@inwind.it

Received 18 January 2002; Revised 15 November 2002; Accepted 21 November 2002.

Abstract

The purpose of this study was to determine the maximum-tolerated dose of gemcitabine plus mitoxantrone in women with metastatic breast cancer (MBC) and to evaluate activity and toxicity of this combination in a phase II trial. Sixty-three patients with MBC, previously treated with chemotherapy including anthracycline and/or taxanes, were treated with mitoxantrone 10 or 12 mg m^-2 intravenously on day 1 plus gemcitabine in escalating doses from 600 to 1200 mg m^-2 intravenously on days 1 and 8, every 3 weeks. In phase I, on 23 patients entered on study, dose-limiting toxicity occurred at the dosage of 1200 mg m^-2 gemcitabine and 10 mg m^-2 mitoxantrone, with three out of five patients developing grade 4 neutropenia. In phase II, with gemcitabine administered at 1000 mg m^-2 and mitoxantrone at 10 mg m^-2, 12 (30%) out of 40 assessable patients responded, even if no complete response was obtained. Moreover, stable disease was observed in eight (20%) patients. The median time to treatment failure was 22 weeks (range, 2–33), and median survival was 42 weeks (range, 2–92). Grade 3 and 4 neutropenia were observed in 12 (30%) and one (2.5%) cases respectively; grade 3 thrombocytopenia was observed in two patients (5%), grade 2 mucositis in two patients (5%), grade 3 anaemia in two patients (5%), grade 3 alopecia in one patient (2.5%) and asymptomatic cardiotoxicity in three patients (8%), respectively. In conclusion, the doses of 10 mg m^-2 (day 1) for mitoxantrone and 1000 mg m^-2 for gemcitabine (days 1–8) every 3 weeks resulted active and safe in MBC. Further investigations in less heavily pretreated patients are warranted.