Treatment of advanced breast cancer with gemcitabine and vinorelbine plus human granulocyte colony-stimulating factor

Purpose. A phase II trial was performed to investigate the efficacy and tolerance of gemcitabine, vinorelbine, and recombinant human granulocyte colony-stimulating factor (G-CSF) in advanced breast cancer. Patients and methods. Between April 96 and August 97, 60 patients entered this trial. Forty-five patients were previously untreated and 15 patients had failed previous palliative chemotherapy with (n = 10) or without anthracyclines (n = 5). Therapy consisted of gemcitabine 1000 mg/m(2) on days 1 + 15 + 21 and vinorelbine 40 mg/m(2) on days 1 + 21, both diluted in 250 ml saline and infused over 30 min. G-CSF was administered at 5 mu g/kg/day subcutaneously from days 2-6 and 22-26. Courses were repeated every 5 weeks. Treatment was continued in case of response or stable disease until a total of six courses. Results. The overall response rate was 55.5% for patients who had not received prior palliative chemotherapy (95% confidence interval, 40%-70.3%), including 5 CR (11.1%) and 20 PR (44.4%) 12 patients (27%) had stable disease (SD), and 8 (18%) progressed. Second-line treatment with this regimen resulted in 6/15 (40%) objective remissions, 5 had SD, and 4 PD. The median time to progression was 9.5 months (range, 1.5-28) in previously untreated patients, and 7.0 months (range, 2-23) in those who had failed prior chemotherapy. After a median follow-up time of 15 months, 44 patients (73%) are still alive with metastatic disease. Myelosuppression was commonly observed, though WHO 3 and 4 neutropenia occured in only 9 (15%) and 2 patients (3%), and was never complicated by septicaemia; grade 3 anemia was noted in 2 patients. Severe (WHO grade 3) nonhematologic toxicity was rarely observed, and included nausea/emesis in 3 and constipation in 2 patients. Conclusions. Our data suggest that gemcitabine and vinorelbine plus G-CSF is an effective and tolerable first- as well as second-line combination regimen for treatment of advanced breast cancer.