Background:
Chronic oral tegafur (a 5-fluorouracil prodrug) modulated by folinic acid has antitumor activity in patients with metastatic breast carcinoma resistant to 5-fluorouracil or doxorubicin-based regimens. in this study, bolus 5-fluorouracil was substituted with chronic oral tegafur and folinic acid in a cyclophosphamide, methotrexate, and 5-fluorouracil-based regimen to study the activity of this novel regimen in patients with advanced breast carcinoma.
Methods:
This study was comprised of patients with advanced breast carcinoma and measurable or evaluable disease. patients with prior chemotherapy were eligible. the regimen was comprised of cyclophosphamide, 600 mg/m2, and methotrexate, 40 mg/m2, both given intravenously on day 1, and tegafur, 750 mg/m2, with folinic acid, 45 mg/day, both given orally in 3 daily fractions on days 2-14, every 3 weeks.
Results:
Forty-seven patients were included, 44 of whom were fully assessable. three patients (7%) achieved a complete remission and 17 (38.6%) achieved a partial remission, for an objective response rate of 45.5% (95% confidence interval, 29-59%). the median duration of response was 11 months. in previously untreated patients the response rate was 54.5%. in patients previously treated with anthracycline or 5-fluorouracil-based regimens the response rates were 41% and 39%, respectively. sixteen patients (36.4%) had disease stabilization. the median overall time to progression was 10 months. toxicities usually were mild and were comprised of leukocytopenia, mucositis, emesis, and diarrhea.
Conclusions:
Chronic oral tegafur and folinic acid combined with intravenous cyclophosphamide and methotrexate at the dose and schedule used in the current study has significant antitumor activity both as first-line chemotherapy as well as in other patients with advanced breast carcinoma who had prior chemotherapy. this regimen is well tolerated, with gastrointestinal toxicity being the most frequent and dose-limiting toxicity.