PROTRACTED CONTINUOUS-INFUSION OF 5-FLUOROURACIL IN COMBINATION WITH DOXORUBICIN, VINCRISTINE, AND ORAL CYCLOPHOSPHAMIDE IN ADVANCED BREAST-CANCER

Several studies suggest that protracted continuous infusion constitute s an important way to optimize the dose and the efficacy of 5-fluorour acil (5-FU) in metastatic cancer. Eighty-three women aged 27-76 (media n age 55) with metastatic breast cancer were treated every 4 weeks wit h a continuous ambulatory venous infusion of 5-FU 350 mg/m(2)/day and oral cyclophosphamide 100 mg/m(2)/day over 15 days. The continuous the rapy was associated with a weekly administration of vincristine (0.8 m g/m(2)) and doxorubicin (15 mg/m(2)) on day 1, day 8, and day 15. Cycl es were repeated every 28 days. Thirty-four patients were treated in f irst-line metastatic chemotherapy and 49 in second-line. Toxicities in cluded: mucositis (grade greater than or equal to 2) 23%, diarrhea (gr ade greater than or equal to 2) 7%, a hand-foot syndrome (grade greate r than or equal to 2) 9%, alopecia (grade 3) 21%, neurological (grade greater than or equal to 2) 4%, grade 3 and 4 leukopenia 29%, and grad e 3 and 4 thrombopenia 8%. Heart toxicity was only 3%. Catheter infect ion was observed in I case and 7 patients experienced thrombosis. The overall objective response rare (OR) was 48% and the complete response rate was 23%. The median duration of response was 10 months. The medi an survival was 16 months. Activity was better in naive than pretreate d women (respectively, 55% and 42% of OR, p = 0.21). Analysis of respo nses according to the metastatic sites shows the pronounced efficacy o n soft tissus diseases (skin recurrences 42%, lymph nodes 52%), and al so in visceral metastases (hepatic 36%, lung 34%).