Docetaxel in combination with 5-fluorouracil in patients with metastatic breast cancer previously treated with anthracycline-based chemotherapy: a phase I, dose-finding study

This phase I study evaluated the maximum tolerated dose. dose-limiting toxi city and recommended dose of docetaxel in combination with 5-fluorouracil ( 5-FU) in patients with metastatic breast cancer previously treated with ant hracycline-based chemotherapy. 32 patients received docetaxel at 60, 75, 85 or 100 mg/m(2) by 1-h intravenous (i.v.) infusion, followed, after a 1-h i nterval, by 5-FU at 250, 350, 500 or 750 mg/m(2)/day by continuous infusion over 5 days every 3 weeks. Dose-limiting stomatitis defined the maximum to lerated dose at a docetaxel dose of 100 mg/m(2) with 5-FU 750 mg/m(2)/day. None of 5 patients treated at the previous dose level (docetaxel 85 mg/m(2) with 5-FU 750 mg/m(2)/day) had a dose-limiting toxicity in the first cycle , and this was, therefore, considered the recommended dose. The combination was generally well tolerated. Grade 4 neutropenia was common (29 patients; 91%), but no patient experienced febrile neutropenia of duration > 3 days requiring i.v. antibiotics. An objective response was achieved by 18 patien ts overall (56%), and in 4 out of 5 patients treated with the determined re commended dose. No pharmacokinetic interaction between docetaxel and 5-fluo rouracil was apparent. The activity of docetaxel 85 mg/m(2) with 5-fluorour acil 750 mg/m(2)/day will be explored more extensively in phase II studies of patients with metastatic breast cancer previously treated with anthracyc line-based chemotherapy. (C) 2000 Elsevier Science Ltd. All rights reserved .