A phase I/II trial of docetaxel in combination with epirubicin and continuous infusion 5-fluorouracil in patients with recurrent breast cancer. Epirubicin is known to have a dose limiting cardiac toxicity. A phase I trial of epirubicin in combination with 5-FU (arm A) and a phase II study of epirubicin and docetaxel (arm B) were undertaken to reduce the cardiac toxicity without compromising antitumour efficacy. Patients with metastatic breast cancer were recruited. Patients received 5-FU by a continuous intravenous (IV) infusion at 600 mg/m2/day on days 1-7 with either epirubicin (30 mg/m2 on day 1) or docetaxel (60 mg/m2 on day 1). The drug dose of the other component was escalated. The initial dose level of epirubicin was 20 mg/m2 (arm A) and 25 mg/m2 (arm B). The next dose level was 30 mg/m2 (arm A) and 35 mg/m2 (arm B). The subsequent dose level was 40 mg/m2 for epirubicin (arm A) and 45 mg/m2 for docetaxel (arm B). If there was no grade 3/4 non-haematological toxicity, the next dose level was considered for further evaluation. If two patients experienced a grade 3/4 non-haematological toxicity, it was defined as the maximum tolerated dose (MTD) and the dose for the next patient was reduced by 10%. If the dose was reduced further, it was designated as the recommended dose (RD) and the dose escalation discontinued. 15 patients were enrolled, of whom 12 were included in the phase II study. In arm A, the MTD and RD were 30 mg/m2 for epirubicin and 35 mg/m2 for 5-FU, respectively. In arm B, the MTD and RD were 45 mg/m2 for docetaxel and 600 mg/m2/day for 5-FU, respectively. All the other patients in this trial received 35 mg/m2 of epirubicin. There were no treatment related deaths and toxicity was manageable. Objective responses were observed in five of the 12 patients with a response rate of 41.6%. One patient had stable disease in both arms. The combination of continuous infusion 5-FU, epirubicin, and docetaxel was well tolerated. Toxicities were manageable without any deaths. In both arms, the RD was at least 30% below the MTD. The recommended doses of epirubicin, 5-FU, and docetaxel were 35 mg/m2, 600 mg/m2/day, and 45 mg/m2, respectively. The continuous infusion of 5-FU and epirubicin combined with docetaxel can be considered a promising combination for further evaluation.