The investigators hypothesize that lesional, site-restricted controlled-release polymer delivery of therapeutic agents, which demonstrate AIDS-related Kaposi's sarcoma (AIDS-KS) cytocidal and angiostatic activities, will markedly improve management of oral and perioral AIDS-KS. AIDS-related Kaposi's sarcoma is the most common AIDS-related malignancy. AIDS-KS can affect both mucosa and skin, with intraoral disease often behaving aggressively, resulting in extensive soft tissue and bone destruction. This study is primarily directed at patients with early or limited disease consisting of cutaneous and oral lesions. AIDS-KS cells show high autologous production of growth promoting cytokines. Therefore existing AIDS-KS lesions can function not only to promote their own growth, but also to stimulate development of new tumor foci. Prompt intervention in patients with limited disease will interrupt the autologous KS growth promoting cascade. Current AIDS-KS treatments include surgery, radiation, and systemic chemotherapy, all of which are associated with significant morbidity. Because AIDS-KS is characterized by prominent neovascularization and AIDS-KS cellular proliferation, the treatment modalities selected will be angiostatic and chemotherapeutic. The three chemotherapeutic agents are doxorubicin, bleomycin and vincristine. The angiostatic agent is TNP-470. These three chemotherapeutic agents were selected because this combination has shown good results in systemic AIDS-KS chemotherapy trials. Also, data from the investigator's laboratory has shown that in vitro cultured AIDS-KS cells are susceptible to oxidant stress and they expect that compounds which generate reactive oxygen intermediates, i.e., doxorubicin and bleomycin, will have selective cytotoxicity. The goals of this proposal are: 1) evaluate drug cytotoxicity and interaction in AIDS-KS and related human cells in monolayer culture, 2) determine the drug concentrations that are cytotoxic to the AIDS-KS cells in AIDS-KS tissue explants, 3) develop slow release drug delivery vehicles, 4) evaluate the drug delivery vehicles in a rabbit model, 5) conduct a Phase I/II clinical trial in individuals with oral and perioral AIDS-KS. In addition to these goals to improve treatment for oral AIDS-KS, the investigators anticipate that results regarding site-restricted drug delivery and local pharmacodynamics will be applicable to local delivery of other agents that are currently used in AIDS-KS treatment.
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