LIPOSOMAL DOXORUBICIN IN THE TREATMENT OF ADVANCED AIDS-RELATED KAPOSI-SARCOMA

Neither single-agent therapy nor any combination treatment has been sa tisfactory enough to be regarded as standard in systemic advanced Kapo si sarcoma. In an attempt to achieve high efficacy in combination with low toxicity, we used a new liposomal formulation of doxorubicin. Pha rmacologic data had established a long plasma half-life, an increased accumulation in tumor tissue, and a decrease in uptake by tissues such as liver, spleen, and bone marrow. In a phase I/II open-label, dose-e scalating trial 40 male AIDS patients with advanced Kaposi sarcoma wer e enrolled to receive intravenous ''stealth'' liposomal doxorubicin bi weekly at doses of 10 mg/m(2) (n = 10), 20 mg/m(2) (n = 27), and 40 mg /m(2) (n = 3). The median CD4 count at baseline was 25/mu L. After six cycles (12 weeks), 39 patients were evaluable. Three patients (7.5%) showed a complete response, which was histologically confirmed. A part ial response was documented in 33 patients (85%). Stable disease was o bserved in three patients (7.5%). During a median treatment duration o f 25 weeks, four patients developed stomatitis (10%), and four patient s (10%) experienced alopecia. The most frequent hematologic toxicity w as neutropenia. Grade 4 neutropenia was seen in 42.5%, and grade 3 tox icity was seen in 30%. Toxicity was dose-dependent and more frequent i n the 40 mg/m(2) stratum. During a median observation period of 25 wee ks, opportunistic infections occurred in 57.5% of the patient populati on. We conclude that liposomal doxorubicin at dose levels of 10 and 20 mg/m(2) is safe and effective for treatment of advanced Kaposi sarcom a in AIDS. A controlled trial comparing liposomal doxorubin to convent ional combination therapy is underway.