Phase II trial of liposome-encapsulated doxorubicin, cyclophosphamide, and fluorouracil as first-line therapy in patients with metastatic breast cancer

Purpose: To determine the efficacy and safety profile, including the risk for cardiac toxicity, of lipasome-encapsulated doxorubicin (TLC D-99), fluorouracil (5FU), and cyclophosphamide as first-line chemotherapy in patients with metastatic breast cancer (MBC). Patients and Methods: Forty- one women were registered in this phase II study. All patients had measurable disease and no previous chemotherapy for MBC. Treatment consisted of TLC D- 99 60 mg/m² and cyclophosphamide 500 mg/m² on day 1 and 5-FU 500 mg/m² on days 1 and 8 every 3 weeks. Serial cardiac monitoring, including endomyocardial biopsies, was performed. Results: The overall response rate was 73% (95% confidence interval, 57% to 86%). The median duration of response was 11.2 months, the median time to treatment failure was 8.1 months, and the median overall survival duration was 19.4 months. The median number of cycles per patient was 10. The median cumulative dose of TLC D-99 was 528 mg/m². Ten patients required hospitalization for febrile neutropenia. Nausea/vomiting, stomatitis, and fatigue higher than grade 2 occurred in 12%, 15%, and 41% of patients, respectively. Twenty-one patients reached a cumulative doxorubicin dose greater than 500 mg/m². Three patients (7%) were withdrawn from the study due to protocol-defined cardiac toxicity, two because of a decrease in left ventricular ejection fraction to ≤ 40%, and one because her endomyocardial biopsy result was grade 1.5. One patient had congestive heart failure that was probably nonanthracycline related. Conclusion: This chemotherapy regimen, including TLC D-99, was highly active against MBC and associated with low cardiac toxicity despite high cumulative doses of daxorubicin.