Randomized phase II trial of infusional fluorouracil, epirubicin, and cyclophosphamide versus infusional fluorouracil, epirubicin, and cisplatin in patients with advanced breast cancer

Purpose: We previously developed an inpatient regimen that consisted of infusional fluorouracil (5-FU), epirubicin, and cisplatin (ECisF), with a response rate of 86% in advanced breast cancer. The current phase II 2:1 randomised study investigated whether cyclophosphamide can be substituted for cisplatin (ECycloF) to reduce toxicity and allow the regimen to be administered on an outpatient basis without loss of efficacy. Patients and Methods: Ninety-six women (median age, 49 years; range, 28 to 73) with breast cancer (59 metastatic, 37 locally advanced) received continuous infusional 5-FU (200 mg/m(2)/d via Hickman line) and six cycles of epirubicin (60 mg/m(2) every 21 days) with either cyclophosphamide 600 mg/m(2) every 21 days (38 metastatic, 24 locally advanced) or cisplatin 60 mg/m(2) every 21 days (21 metastatic, 13 locally advanced). There were no significant differences in patient characteristics between these groups. Results: ECycloF was better tolerated than ECisF in terms of lethargy (P = .005), stomatitis (P = .008), plantar palmar erythema (P = .02), constipation (P < .001), thrombosis (P = .0014), and nausea and vomiting (P = .05). Although there was a trend toward more anemia and leukopenia with ECisF (P = .1), there was no significant difference in the rates of infection. Efficacy was comparable in terms of overall response (69% v 68%), complete response (CR; 13% v 15%), and median progression-free survival (9 v 8 months). Conclusion: ECycloF is an outpatient regimen with a lower incidence of severe nonhematologic toxicity than inpatient ECisF; it has comparable efficacy and is considerably more economical. (C) 1998 by American Society of Clinical Oncology.