Combination of docetaxel and mitoxantrone for the therapy of metastatic breast cancer - a phase I-II study

Background: Taxanes and anthracyclines represent the two most active groups of agents for the treatment of metastatic breast cancer. The aim of this s tudy was to evaluate the safety and toxicity of a combination of mitoxantro ne (M) and docetaxel (D). Patients and Methods: Patients were treated at th ree dose levels: Level I: M = 12 mg/m(2), D = 80 mg/m(2), II: M =14 mg/m(2) , D = 80 mg/m(2), and III: M = 14 mg/m(2), D =100 mg/m(2) each per day ever y three weeks. 36 patients were entered in the study (24 in level I, 6 in l evel II, and 6 in level III). The median age was 55 years (26-68y). 13 pati ents had one, 14 had two, and 9 had three metastatic sites. The patients ha ve had two (median) previous chemotherapy regimens. Results: The number of cycles per patient was 5 (1 -8) and data of 180 cycles are available. Main toxicity without G-CSF was grade IV neutropenia in 66%. Grade III anaemia w as found in two patients and grade III thrombocytopenia was observed in 4 p atients. Non-haematologic grade III toxicities were lethargy, mucositis, di arrhea, nausea, reversible skin changes and in all patients complete alopec ia. No reduction of LVEF and no fluid retention was observed. Overall respo nse rate in 32 evaluable patients was 37% (three complete and 9 partial rem issions), in further 56% stable disease could be documented. In level I 30% , in level II 0% and in level III 66% of the patients responded. Conclusion : The combination of Mitoxantron (12 mg/m(2)) and Docetaxel (80 mg/m(2)) is safe and effective in patients with metastastic breast cancer. It is curre ntly evaluated in a randomized trial.