PACLITAXEL WITH MITOXANTRONE, FLUOROURACIL, AND HIGH-DOSE LENCOVORIN IN THE TREATMENT OF METASTATIC BREAST-CANCER - A PHASE-II TRIAL

Purpose: Paclitaxel is a highly active single agent in the treatment o f breast cancer. However, its optimal incorporation into combination r egimens awaits definition. In this phase II study, we added paclitaxel , administered by 1-hour infusion, to a previously described combinati on regimen that included mitoxantrone, fluorouracil (5-FU), and high-d ose leucovorin (NFL). Patients and Methods: Forty-six patients with me tastatic,breast cancer received the following regimen as first- or sec ond-line treatment: paclitaxel 135 mg/m(2) by 1-hour intravenous (IV) infusion on day 1, mitoxantrone 10 mg/m(2) by IV bolus on day 1, 5-FU 350 mg(2)/m by IV bolus on days 1, 2, and 3, and leucovorin 300 mg IV over 30 to 60 minutes immediately preceding 5-FU on days 1, 2, and 3, Courses were administered at 3-week intervals for a total of eight cou rses in responding patients. Results: Twenty-three of 45 assessable pa tients (51%) had major responses. Previous chemotherapy, and in partic ular previous treatment with doxorubicin, did not affect response rate . The median response duration was 7.5 months, Myelosuppression was mo derately severe, with 76% of courses resulting in grade 3 or 4 leukope nia, Hospitalization for treatment of fever during neutropenia was req uired in 13% of courses, and two patients died as a result of sepsis, Two patients developed severe congestive heart failure after a large c umulative anthracycline dose, Conclusion: This combination regimen was active as first- or second-line therapy for metastatic breast cancer, although its activity compared with other combination regimens or wit h paclitaxel alone is unclear, Myelosuppression was more severe than a nticipated based on previous results with the NFL regimen or with pacl itaxel administered at this dose and schedule as a single agent. The i nfrequent development of cardiotoxicity in these patients suggests tha t the paclitaxel/mitoxantrone combination may not share the problems p reviously reported with the paclitaxel/doxorubicin combination. (C) 19 96 by American Society of Clinical Oncology.