A phase II study of an oxaliplatin/vinorelbine/5-fluorouracil combination in patients with anthracycline-pretreated and taxane-pretreated metastatic breast cancer

The aim of this phase 11 study was to evaluate safety and efficacy of an oxaliplatin/vinorelbine/5-fluorouraciI (FON) combination in anthracycline and taxane-pretreated metastatic breast cancer patients. The following treatment was given: on day 1 of a 21-day cycle, oxaliplatin 130 mg/m(2) (2-h intravenous infusion); on days 1 and 5, vinorelbine [close level 00 1: 17.5 mg/m(2); DL2: 22 mg/M-2]; on days 1-5, continuous infusion 5-fluorouracil (DL1: 600 m/m(2)/day; DL2: 750 mg/m(2)/day). Forty-seven patients were treated (DL1: 43; DL2: 4). Median age was 54 years; 68% had liver metastases, 53% were taxane refractory/resistant and 38% were anthracycline refractory/resistant. Patients received a median of six treatment cycles. Of 46 eligible patients, 16 had partial response; the overall response rate was 34.8% (95% confidence interval 21.3-50.3%), 11 had stable disease lasting more than 4 months. Median follow-up was 13.0 months, median time to progression 5.7 months and estimated overall survival 18.8 months. DL2 was too toxic with three patients having grade 3-4 toxicity, including one death. At DL1, 215 patients (60%) experienced grade 3-4 neutropenia (six febrile neutropenia) and eight had grade 3 oxaliplatin-specific peripheral neuropathy after a median of 646.4 mg/m(2) oxaliplatin (range 124-1619mg/m(2)). Oxaliplatin (1130 mg/m(2), day 1)/vinorelbine (117.5 mg/m(2), days 1,5)/5-fluorouracil (600 mg/m(2) /day, days 1-5) demonstrate encouraging activity and a manageable safety profile in anthracycline- and taxane-pretreated metastatic breast cancer patients.