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

Purpose: To determine the efficacy and safety profile, including the risk f or cardiac toxicity, of liposome-encapsulated doxorubicin (TLC D-99), fluor ouracil (5-FU), 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 stud y. All patients had measurable disease and no previous chemotherapy for MBC . Treatment consisted of TLC D-99 60 mg/m(2) and cyclophosphamide 500 mg/m( 2) on day 1 and 5-FU 500 mg/m(2) on days 1 and 8 every 3 weeks. Serial card iac monitoring, including endomyocardial biopsies, wets 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 rime 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 wets 528 mg/m(2). Ten patients required hospit alization for febrile neutropenia. Nausea/vomiting, stomatitis, and fatigue higher than grade 2 occurred in 12%, 15%, and 41% of patients, respectivel y. Twenty-one patients reached a cumulative doxorubicin dose greater than 5 00 mg/m(2). Three patients (7%) were withdrawn from the study due to protoc ol-defined cardiac toxicity, two because of a decrease in left ventricular ejection fraction to less than or equal to 40%, and one because her endomyo cardial biopsy result was grade 1.5. One patient had congestive heart failu re that was probably nonanthracycline related. Conclusion: This chemotherapy regimen, including TLC D-99, was highly activ e against MBC and associated with low cardiac toxicity despite high cumulat ive doses of doxorubicin. I Clin Oncol 17:1425-1434. (C) 1999 by American S ociety of Clinical Oncology.