Gay Men's Health Crisis: Treatment Issues, Volume 8 no. 9 - October 1994
Gabriel Torres, M.D.

Liposomal Chemotherapy

Data on the use of chemotherapeutic agents encapsulated within liposomes (tiny fat globules that regulate the passage of the entrapped drug from the blood stream to specific sites - see April 1994 Treatment Issues), were presented by various groups of investigators who have successfully used these agents in patients with AIDS-related KS.

- DOX-SL: The best results to date were seen in the International DOX-SL Study,[1] a multicenter European and Australian phase II/III study of 247 KS patients. DOX-SL is a preparation of doxorubicin encapsulated in "stealth" liposomes that deliver significantly greater quantities of the drug to the KS lesions. "Stealth" liposomes incorporate a protective polyethylene glycol (PEG) coating allowing them to circulate in the bloodstream for up to 48 hours or more. Conventional uncoated liposomes are cleared from the blood in a few hours. (By comparison, unencapsulated - "free" - drug disappears from blood in a matter of minutes.)

The patients were treated with DOX-SL intravenously using a 30 minute infusion every two weeks. Patients were started at 10 or 20 mg/m2 of body area, and the dose was titrated upward if KS lesions failed to respond. Two-thirds of the trial participants received at least six infusions. Of the 133 for whom response data are available, three (1.8 percent) attained a complete response, 81 (48.5 percent) a partial response and 38 (22.8 percent) had stable disease. Partial or complete responses were typically seen within two or three cycles of DOX-SL. Side effects included nausea (25 percent), vomiting (13.9 percent), stomatitis (11.8 percent), diarrhea (24.9 percent) and hair loss (11.8 percent). Significant neutropenia occurred in 17.9 percent of all treatmentcycles whereas anemia and thrombocytopenia occurred in 21.6 percent and 12 percent of all cycles, respectively.

On September 7, 1994, Liposome Technology, Inc., the manufacturers of DOX-SL, filed a New Drug Application (NDA) with the U.S. Food and Drug Administration for the treatment of KS in people with AIDS who cannot tolerate or have failed conventional chemotherapy. (Until this application is approved, people with KS and intolerant to ABV, a standard anti-cancer therapy, can receive DOX-SL through a special open-label trial accessible through 30 sites nationwide. Call Liposome Technology at 415/323-9011 for more information.)

- Daunoxome: Daunoxome is the drug daunorubicin encapsulated by a conventional liposome. The first phase II study of daunoxome was presented in Yokohama.[2] Through February 1994, 42 patients had been treated with Daunoxome every two weeks. One-third of the patients had a partial response and the other two-thirds had stable disease. The median duration of the response with the 40 mg dose was 7.5 to nine weeks, depending on the dose. The main side effect was neutropenia, which could be managed with G-CSF (Neupogen).

Interleukin-4

The Yokohama Conference heard the first clinical data on the use of interleukin-4 (IL-4) in patients with KS.[3] IL-4 promotes CD4 cell proliferation and also suppresses interleukin-6 production - as well as KS cells in culture. IL-6 is found in high levels in patients with KS and is implicated in the pathogenesis of KS lesions.

The phase I/II study (ACTG 224) enrolled patients with biopsy-proven KS who had IL-4 administered subcutaneously in escalating doses. So far, thirteen trial participants have received one of two dose levels. Side effects such as fever, fatigue and headaches were very common. Only three patients experienced a partial response. The dose limiting toxicity to date has been neutropenia. On the other hand, significant decreases (60 percent) in HIV p24 antigen levels were observed in all patients, which raises the possibility that IL-4 is useful as an anti-HIV drug.

1 Goebel FD et al. Tenth international conference on AIDS abstract book. Aug 7-12 1994; I(abstract PB0123):174.

2 Wernz JC et al. Tenth international conference. I(abstract 046B):18.

3 Miles SA et al. Tenth international conference. I(abstract 159B):46.

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