A phase II trial of liposomeencapsulated doxorubicin in advanced measurable breast cancer

Previous animal studies have demonstrated that liposome-encapsulated doxorubicin (LED) has substantially less cardiac toxicity than the free drug, but retains antitumor activity. In a Phase I clinical study of LED the maximum tolerated dose was 90 mg/m2 and the dose-limiting toxicity was granulocytopenia. We have now treated 20 patients who had advanced measurable breast cancer with LED at a dose of 75 mg/m2 every 3 weeks as an intravenous infusion. Objective disease regressions occurred in nine of these patients and five of these responses were complete in the index lesion. The mean duration of the responses was 7 months. Hematologic toxicity consisted of grade 1-2 granulocytopenia in some patients. Gastrointestinal toxicity and mucositis were mild and tolerable. Alopecia occurred in all patients and usually was complete. Twelve of the 20 patients received cumulative LED doses >400 mg/m2 and were evaluated with radionuclide ventriculogram (RVG). In eight of these 12 patients the total dose was >500 mg/m2 and endomyocardial biopsies were performed in five of the eight. Of the 5 patients who had endomyocardial biopsies, four were Billingham grade 0, while one (cumulative LED dose of 750 mg/m2) had grade 1 changes with mild myofibrillar loss and dilatation of the sarcoplasmic reticulum involving less than 5% of the cardiac myocytes. These data show that LED is an effective antitumor agent in breast cancer and produces very little cardiac damage after cumulative doses of 500-880 mg/m2.