Mitoxantrone, 5-fluorouracil and high-dose leucovorin (NFL) in the treatment of metastatic breast cancer: randomized comparison to cyclophosphamide,methotrexate and 5-fluorouracil (CMF) and attempts to improve efficacy by adding paclitaxel

The combination of mitoxantrone (12 mg/m² i.v., day 1) 5-fluorouracil (350 mg/m² i.v. days 1–3) and leucovorin (300 mg i.v. days 1–3) is an active and well-tolerated regimen for metastatic breast cancer. We compared this regimen to a standard CMF regimen (cyclophosphamide 600 mg/m² i.v. day 1; methotrexate 40 mg/m² day 1; 5FU 600 mg/m² i.v. day I) in a randomized, phase II study. One hundred and twenty-eight women receiving first-line chemotherapy for metastatic breast cancer were treated. NFL produced lugher response rates (45% vs. 26%) and longer remissions (9 months vs. 6 months) than did CMF; overall survival was not different (19 months vs. 16 months). Both regimens were well tolerated. In an attempt to improve efficacy, we added paclitaxel(l35 mg/m² i.v. 1-h infusion) to the NFL regimen. Although this regimen was active (51 % response rate in first-second-line treatment], myelosuppression was greater than expected. These results confirm the utility of NFL as an active, well-tolerated regimen for the palliative treatment of metastatic breast cancer.