Seattle Treatment Education Project (STEP) Perspective, Vol. 5, No. 2 -

Daunorubicin is a chemotherapy agent which has been used in the treatment of KS. Unfortunately, side effects limited the use of the drug in many individuals. Now, an intravenous formulation of daunorubicin, called Daunoxome, that has been encapsulated in targeted lipsomes is under investigation. A phase II trial enrolled 22 individuals, 20 of whom had extensive KS (more than 25 skin lesions, adenopathy, lymphadema, and/or visceral involvement) and two individuals with minimal KS. The participants received 40 mg/m2 of intravenous Daunoxome every two weeks. The participants were evaluated after two treatments, and those with subsequent breakthrough were dose escalated to 60 mg/m2. One individual had a complete remission, 20 had a partial responses, and one had stable disease. The most common side effect was mild nausea, seen in 20% of the participants. Moderate hematological toxicity occurred in about 10% of the individuals. These results indicate that Daunoxome is an effective treatment for KS, with limited toxicity. A phase III trial is underway (WS-B15-3).

In an attempt to reduce toxicity, liposomal encapsulation of another chemotherapeutic agent, doxorubicin, is also being researched (Doxil). In a phase I/II open study, 40 individuals with advanced KS (median CD4 count of 27) received intravenous infusions of Doxil at doses of 10 mg/m2 (10 participants), 20 mg/m2 (27), and 40 mg/m2 (three). The mean duration of treatment was 25 weeks. All individuals showed considerable decrease in nodularity of skin lesion within two to four weeks, with total flattening in 25%. No new lesions appeared in any participants. All nine participants with pulmonary KS experienced partial remission. The main complaint from participants was hair loss occurring in 13%. All individuals on the 40 mg/m2 dose were switched to 20 mg/m2 due to this side effect. Fever and malaise occurred in 12.5% of the participants for one day following the infusion. The investigators concluded that Doxil appeared to be a safe and effective treatment for advanced KS, with efficacy seen in all participants, including GI and pulmonary involvement (WS-B15-6). Similar results were seen in other studies (PO-B12-1573, PO- B12-1574, PO-B12-1613).

CD8 cell expansion is another novel therapy being studied. CD8 cells are removed and expanded with recombinant interleukin-2 (IL-2) for 14 to 21 days. Then the cells are infused back into the body, and IL-2 therapy is given for five days. (See related article in this issue for more detailed information.) Of the 10 enrolled participants, six have completed at least three of the five planned cell expansions. Five of the six individuals have had partial responses as defined by overall reduction of at least 25% in tumor load, typically a central flattening or resolution of lesions. In two of the participants, new lesions have occurred during therapy (WA-B15- 2). Further results from this trial will be eagerly anticipated.

A popular underground therapy for KS is the use of Retin-A cream, with positive anecdotal reports. A small study using systemic all-trans retinoic acid (ATRA) was presented. Seven individuals with stage IIa disease received two mg/kg orally a day in three or four divided doses. Six of the seven participants showed a clinical response. Additionally, ATRA appeared to have a protective effect against the development of new lesions. Side effects included dryness of the skin and myalgia in one individual and headache in two participants. Minor increases in liver enzyme activity and triglycerides were noted in three individuals (PO-B12- 1562).