FOLINIC ACID, 5-FLUOROURACIL BOLUS AND INFUSION AND MITOXANTRONE WITHOR WITHOUT CYCLOPHOSPHAMIDE IN METASTATIC BREAST-CANCER

60 patients with metastatic breast cancer were entered in a phase II s tudy using folinic acid, 5-fluorouracil bolus and infusion and mitoxan trone with or without cyclophosphamide. 47 had measurable visceral met astases and 13 had exclusively bone metastases. 36 had received previo us adjuvant or metastatic treatment (33/36 with anthracycline-based re gimens). Overall response rate in visceral metastatic patients was 57. 1% [95% confidence interval (CI) 35.4-78.8%]; 45.5% and 70% in previou sly and non-previously treated patients, respectively; duration of res ponse was 9 and 13 months, respectively. 10 out 13 patients with exclu sive bone metastases improved for a median time of 18 months. Median s urvival was 22 months for the 60 patients; 18 and 31 months for previo usly and non-previously treated patients, respectively. Cyclophosphami de was scheduled only in the absence of nadir grade 4 neutropenia. How ever, this toxicity occurred in the first 7 patients. For this reason, we chose to avoid cyclophosphamide in patients over 60 years, or with a performance status of 1-2, or who had received previous chemotherap y. Overall, cyclophosphamide was stopped due to nadir grade 4 neutrope nia in 17/24 patients for whom this drug was planned. When mitoxantron e, 5-fluorouracil and folinic acid were used at the doses scheduled, t he addition of cyclophosphamide appeared feasible in only about 25% of the patients. Furthermore, survival was identical for patients receiv ing or not receiving cyclophosphamide. Therefore, cyclophosphamide doe s not contribute substantially to this regimen. This study confirms th e value of folinic acid, 5-fluorouracil and mitoxantrone in metastatic breast cancer.