Phase I/II trial of weekly epidoxorubicin and docetaxel (wED) in the neoadjuvant and palliative treatment of patients with breast cancer.

PURPOSE: Anthracyclines and taxanes are the most active cytotoxic agents in the treatment of breast cancer. Based on observations with weekly administration of paclitaxel which results in better tolerability and higher dose intensity as compared with 3-weekly schedules, we designed a phase I/II trial with weekly epidoxorubicin and docetaxel (wED) for the preoperative and palliative treatment of patients with breast cancer. PATIENTS AND METHODS: A group of 33 female patients (20 neoadjuvant and 13 palliative) were treated with weekly epidoxorubicin (25-35 mg/m(2)) as a short i.v. infusion followed by docetaxel (25-40 mg/m(2)) as a 1-h i.v. infusion once a week for 6 weeks followed by 1 week off therapy, without G-CSF support. Sequential cohorts of patients were treated with epirubicin and docetaxel at the following dose levels: 25/25, 25/30, 30/30, 30/35, 35/35, and 35/40 mg/m(2).
RESULTS: Patients received a total of 74 courses (median 2, range 1-4 courses) of this therapeutic regimen. The maximum tolerated dose occurred at the dose level combining 35 mg/m(2) of epidoxorubicin and 40 mg/m(2) of docetaxel, with the dose-limiting toxicity being neutropenic fever in two patients at dose level 6.
CONCLUSIONS: The wED regimen is a feasible, safe, and highly active combination chemotherapy for advanced breast cancer. We recommend epidoxorubicin 30 mg/m(2) and docetaxel 35 mg/m(2) for further trials because of the high incidence of neutropenic fever and lymphocytopenia of WHO grade IV at dose levels 5 and 6.