Combined 5-fluorouracil infusion with fractionated epirubicin and cyclophosphamide in advanced breast cancer

5-Fluorouracil (5-FU) given by continuous infusion (c.i.) allows higher dos e delivery, causes less myelosuppression, and may interfere with repair of DNA damage caused by epirubicin and cyclophosphamide. With this rationale, we conducted a phase II study to test the activity and toxicity of 5-FU c.i ., epirubicin, and cyclophosphamide in patients with metastatic breast canc er (MBC). Twenty-eight patients with MBC were entered in the trial. 5-FU (2 00 mg/m(2)) was administered by c.i. from day 1 to day 20. Epirubicin (35 m g/m(2)) and cyclophosphamide (400 mg/m(2)) were administered from day 2 to day 4, every 4 weeks. All patients were evaluable for response and toxicity . A total of 125 courses of chemotherapy were administered, with a median o f 4 per patient (range: 2-6). Toxicity, assessed using World Health Organiz ation criteria, was as follows: nausea and vomiting grade III-IV occurred i n 36%, alopecia (grade III) in 86%, neutropenia (grade III-IV) in 50%, and cardiac toxicity grade I-H in 11% of patients. Five patients (17.9%) had a complete response to therapy, and 16 (57.1%) had a partial response (respon se rate 75%, 95% CI 55-89%). Disease stability and progression occurred in 4 (14.3%) and 3 (10.7%) patients, respectively. Median time to progression was 13.1 months (range: 3.4-66.9+), and median survival time was 27.7 month s (range: 5.4-67.1+). Outpatient treatment with combined 5-FU c.i., epirubi cin, and cyclophosphamide shows high activity in advanced breast cancer and gives prolonged remission with acceptable toxicity.