Purpose: To determine the maximum tolerated doses (MTD) and dose-limiting toxicities (DLTs) of vinorelbine (VNR) with fixed doses of cyclophosphamide (CPM) and 5-fluorouracil/leucovorin (5-FU/LV) in patients with metastatic breast cancer (MBC) pretreated with anthracyclines and taxanes.
Patients and methods: Eighteen patients with MBC pretreated with anthracyclines and taxanes were enrolled. VNR was administered as a 10-min intravenous infusion (i.v.) on day 1 at escalated doses with CPM 300 mg/m2 i.v. bolus and LV 500 mg/m2 as a 2-hour i.v. infusion, followed by 5-FU 1500 mg/m2 as a 22-hour continuous infusion (c.i.) for two consecutive days. Treatment was repeated every two weeks.
Results: At the dose of VNR 22.5 mg/m2 without rhG-CSF and 25 mg/m2 with rhG-CSF support, the DLT had been reached. Grade 3 or 4 neutropenia occurred in six (33%) patients and in fourteen (27%) cycles with no episode of febrile neutropenia. One (5.5%) patient developed grade 4 thrombocytopenia. Grade 3 neurotoxicity occurred in two patients and grade 2 and 3 asthenia in five (28%).
Conclusion: The recommended doses for phase II studies are 20 mg/m2 for VNR (22.5 mg/m2 with rhG-CSF support) and 300 mg/m2 for CPM on day 1, with 500 mg/m2 for LV and 1500 mg/m2 for 5-FU on days 1 and 2.