High-Dose Mitoxantrone and Cyclophosphamide Without Stem Cell Support in Patients with High-Risk and Advanced Breast Carcinoma - A Phase II Multicentric Trial

BACKGROUND. Currently employed high-dose regimens for patients with breast carcinoma consist mainly of single-cycle combinations of alkylating agents. In a previous Phase I trial, the authors developed a tandem high-dose comb ination of two cycles of mitoxantrone and cyclophosphamide for the treatmen t of patients with metastatic breast carcinoma (MBC) and high-risk breast c arcinoma (HRBC). Treatment was delivered with granulocyte-colony stimulatin g factor (G-CSF) but without stem cell support to avoid potential tumor cel l reinfusion. The objective was to validate the safety and obtain prelimina ry efficacy assessment of this combination in a Phase II trial. METHODS. Fifty-three patients were included: 27 patients with MBC and 26 pa tients with HRBC. After standard induction treatment, patients received two cycles of mitoxantrone 25 mg/m(2) and cyclophosphamide 4000 mg/m(2) separa ted by a 4-week interval. Patients received G-CSF and ciprofloxacin until h ematologic recovery. Follow-up was performed in an outpatient setting. RESULTS. One hundred one of 106 projected cycles (95%) were delivered. The mean dose intensities achieved were mitoxantrone 5.8 mg/m(2) per week and c yclophosphamide 933 mg/m(2) per week. Infection developed in 46% of the cyc les, and platelet transfusions were required in 42%. Nonhematologic toxicit y was mainly Grade 3 emesis. There were no toxic deaths. In 17 evaluable pa tients with MBC, 13 patients (77%) had response improvements, including 7 c omplete responses (41%). CONCLUSIONS. Treatment with two cycles of mitoxantrone 25 mg/m(2) and cyclo phosphamide 4000 mg/m(2) with G-CSF but without stem cell support was well tolerated. The dose intensities achieved approach those obtained with conve ntional high-dose therapy. This combination warrants further investigation as an alternative to conventional high-dose regimens. (C) 2001 American Can cer Society.