Antitumor activity of liposome-encapsulated doxorubicin in advanced breast cancer: phase II study. Previous studies in animals have demonstrated liposome-encapsulated doxorubicin (LED) has substantially less cardiac toxicity than free doxorubicin but retains antitumor activity. In a phase I clinical study of LED, the maximum tolerated dose was 90 mg/m2 and dose-limiting toxicity was considered to have been reached when granulocytopenia was produced. We used LED to treat 20 patients with advanced, measurable breast cancer. LED was given at doses of 60-75 mg/m2 every 3 weeks as an intravenous infusion. Regression of disease was objectively measured in nine patients; in five of these patients, complete regression of the index lesion occurred. The mean duration of the responses was 7 months. Hematologic toxicity consisted of grade 1-2 leukopenia in some patients. Gastrointestinal toxicity and mucositis were generally mild and tolerable. Alopecia occurred in all patients and usually was complete. Twelve patients received cumulative doses of LED of greater than 400 mg/m2 and were evaluated with radionuclide ventriculograms. In eight patients, the cumulative dose was greater than 500 mg/m2, and five had endomyocardial biopsies. Four of these biopsy results were Billingham grade 0, while one (cumulative LED dose, 750 mg/m2) showed grade 1 changes with mild myofibrillar loss and dilatation of the sarcoplasmic reticulum involving less than 5% of cardiac myocytes. Two patients had decreases in left ventricular ejection fraction. One of these patients had received a total dose of LED of 630 mg/m2 and had a decline of 13% in left ventricular ejection fraction, but had no clinical evidence of congestive heart failure and had a Billingham grade 0 endomyocardial biopsy. 