Combination of Docetaxel, Epirubicin and Vinorelbine Administered Every 2 Weeks as First-line Therapy in Patients with Metastatic Breast Cancer: A Dose-finding Study

Aims. To assess efficacy and optimum combination dosage of intravenous docetaxel (T), epirubicin (E) and vinorelbine (N) administered every 2 weeks and without colony stimulating factor (CSF) support in patients with metastatic breast cancer (MBC).Patients and method. Patients (n = 51) with MBC were consecutively assigned to four different dose levels (DL) to receive (in mg/m²): Level I = T35 + E30 + N25; Level II = T30 + E30 + N25; Level III = T30 + E25 + N25; and Level IV = T25 + E25 + N25. Consecutive cycles were delayed if absolute neutrophil and/or platelet counts fell below 1.5 × 10⁹ and 100 × 10⁹l^–1, respectively. Treatment at a given dose level was suspended if 33% or more of patients included in a given cohort had unacceptable toxicity.Results. The patients evaluable for toxicity (n = 48) received 448 cycles (median 9; range 1–23). There was neutropenia G 3–4 in 30 patients (63%) with fever in 3 (6%). The G 2–3 non-hematological toxicities were alopecia in 39 patients (81%), mucositis in 11 (23%), and nausea/vomiting in 8 (17%). There were no toxic deaths. Treatment delay or dose reduction after first cycle occurred in 30% of patients treated in all DLs, except the fourth. Objective response was achieved in 29 of the 47 evaluable patients (58%; 95% CI: 50–66). The median duration of response, time-to-progression and overall survival were 13, 11 (range 8–14) and 20 (range 16–24) months, respectively.Conclusion. The combination of docetaxel, epirubicin and vinorelbine without CSF support ought not to exceed 25 mg/m² every 2 weeks. The efficacy is no greater than other existing regimens for first-line treatment of MBC.