Phase II trial of oral tegafur and folinic acid with mitoxantrone as first-line regimen in patients with metastatic breast cancer

Background: Tegafur acts as a deport form of 5-fluorouracil when administered orally for longs periods of time, since it is an active drug in metastatic breast cancer, with response rates of 29-44%. Biochemical modulation with folinic acid and the addition of mitoxantrone could increase the efficacy of tegafur in patients with metastatic breast cancer, Methods: A prospective phase II trial in patients with previously untreated metastatic breast cancer was carried out. The scheme consisted of mitoxantrone, 12 mg/m(2) intravenous day 1, oral tegafur, 750 mg/m(2)/day divided In three equal doses, and leucovorin 15 mg/8 h orally for days 1-21, given in a 4-week schedule. None patient had received chemotherapy for metastatic breast cancer, although 16 patients had received previous adjuvant chemotherapy, Results: Thirty-four patients were included. Objective responses were achieved in 20 of 32 patients assessable for response, with 1 complete response and 19 partial responses. The objective response rate was 62.5% (95% confidence intervals, 48-76%). The median duration of response was 10 months. Grade III-IV toxicity according to WHO criteria was digestive (nausea/vomiting) in 12.5%, diarrhea in 25% and stomatitis in 25% of patients. Other toxicities were low. Eight patients required dose-reduction. Conclusions: We achieved a significant response rate with the scheme, which was administered on an outpatient basis. It seems to be safe and effective as first-line treatment in metastatic breast cancer, with a short median response duration, The size of the trial does not permit definitive conclusions, and the role of biochemical modulation of tegafur in combination with mitoxantrone remains to be defined.