Combined epirubicin and vinorelbine as first-line therapy in metastatic breast cancer: a pilot study performed by the Danish Breast Cancer Cooperative Group

This pilot study investigated the tolerability and efficacy of increasing doses of epirubicin and vinorelbine as first-line chemotherapy for metastatic breast cancer. Acute toxicity was manageable at all dose levels for combinations of epirubicin 60–90 mg/m2 on day 1 and vinorelbine 15–25 mg/m2 on days 1 and 8 repeated every 3 weeks. Myelotoxicity was the most frequent toxic event, with a significant increase in grade 4 leukopenia from 0% at dose level 1 (60+15 mg/m2) to 26% at dose level 6 (90+25 mg/m2). Signs of acute or chronic cardiotoxicity grades 2–4 were seen in 15% of the patients and included arrhythmia and decreased function. No significant association was established between dose and nonhematological toxicity. Objective responses were observed in 49 of the 99 evaluable patients (49.5%, 95% CI 39.9–59.2), 18 being complete and 31 partial responses. Responses were observed at all six dose levels. In conclusion, acute toxicity was manageable at all dose levels for combinations of epirubicin 60–90 mg/m2 on day 1 and vinorelbine 15–25 mg/m2 on days 1 and 8. In the treatment of advanced breast cancer, improvement of the antitumor efficacy by the addition of vinorelbine to epirubicin remains to be demonstrated in a randomized phase III trial.