| Abstract: |
KS is a clinically heterogeneous tumor that may occur throughout the course of HIV infection. A variety of standard therapeutic approaches are available that can induce tumor regression and provide effective and often long-term KS palliation, but such therapy is not curative. Although advances in the treatment of HIV infection, together with the prophylactic use of antimicrobial agents, aggressive management of acute opportunistic infections, and therapeutic adjuncts such as nutritional support, have contributed to an overall improvement in survival for HIV-infected patients with and without KS, there are as yet no data indicating that specific antitumor therapies result in longer survival for KS patients, possibly because factors other than KS have until recently been the primary survival determinants. The finding that tumor stage is independently correlated with survival93 (Krown SE, et al: unpublished observations) and recent therapeutic advances leading to improvements in overall survival for patients with advanced HIV infection may permit the design of studies to address specifically the effects of current KS treatments on survival in comparably staged patients receiving optimal HIV therapy. Advances in understanding the factors contributing to KS development and progression have suggested a large number of potential targets for therapeutic intervention directed at both viral and host factors. Although tremendous opportunities exist to exploit these new insights for therapeutic benefit, the multiplicity of factors implicated in KS pathogenesis may imply that combinations of approaches targeting different factors may be required for effective or optimal tumor control. In this context, it should probably be no surprise that the antiangiogenesis approaches tested thus far have proved disappointing insofar as their single-agent activity against KS is concerned. The effectiveness of IFN-α against KS may be testimony to its potential activities against multiple factors contributing to endothelial cell proliferation and angiogenesis, and the superior results obtained with IFN-α/nucleoside analogue combination therapy may be taken as further support for the soundness of a multitargeted approach to KS therapy. This type of approach is being developed further through a new trial combining IFN-α, stavudine, and an HIV protease inhibitor, and there exist other potential combinations with similar rationales. It should be cautioned, however, that such combinations involve more than simply combining a seemingly infinite group of agents and that serious potential exists for adverse drug interactions that require careful monitoring in the context of approved protocols.The identification of cells with characteristics suggestive of KS precursors in the circulation of HIV-infected patients considered at high risk for the development of KS25 and the equally intriguing observation that the presence of HHV-8 in peripheral blood mononuclear cells may precede the development of overt KS170 hold promise for the future identification of specific high-risk populations in whom prophylactic strategies could be tested. It is conceivable that such patients would be more likely than those with established, advanced KS to benefit from interventional strategies aimed at blocking the myriad factors that result in KS development. It is likely, however, that such targeted preemptive interventions are many years off and will first require proof of safety and at least some degree of efficacy in established disease. |
