Phase II/III Study Of TretinoinLF In KS

Genzyme has begun a Phase II/III study of Argus Pharmaceuticals' intravenous liposomal product TretinoinLF (all-trans-retinoic acid) in patients with Kaposi's sarcoma. Genzyme is cosponsoring the trial with Argus. The Kaposi's sarcoma study is a multicenter, open-label trial that could involve approximately 120 patients with this AIDS-associated disease. The trial is designed to evaluate the safety and clinical activity of TretinoinLF using two dosing schedules.

A variety of human trials have documented that ATRA and other retinoid compounds are active against numerous cancers, including KS. However, treatment with orally-active ATRA compounds has been associated with a high rate of relapse. The clinical rationale for TretinoinLF rests on the premise that drug resistance to oral forms of ATRA arises from a rapid clearance mechanism in humans which prevents the agent from maintaining therapeutic levels in the circulation.

Genzyme and Argus hope that delivery of ATRA in liposomes by the intravenous route will overcome these limitations, improving delivery to tissues and bypassing the clearance mechanism. Current treatment for the condition begins with alpha interferon, but this gradually declines in efficacy as the patient's immune system declines. Cytotoxic agents are then used, but toxicity usually outweighs treatment benefits.