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Acquired immunodeficiency syndrome-related cancers: the community perspective.

Those individuals who work for acquired immunodeficiency syndrome (AIDS) community-based organizations (treatment education, dissemination, advocacy, and care) and the people with AIDS whom they represent are commonly referred to as the ‘‘AIDS community.’’ While the primary interest of the AIDS community is safe and effective antiretroviral therapy, many of us are concerned with the opportunistic neoplasms that affect approximately 25% of people with AIDS. The community’s perspective on AIDS-related cancers can be summarized as follows: 1) It’s about time the National Cancer Institute (NCI) got its act together. 2) How and when are diseases such as AIDS-related Kaposi’s sarcoma and non-Hodgkin’s lymphoma going to be cured and prevented? 3) Until then, how can we be sure that we will receive the best medical care for these cancers and the underlying human immunodeficiency virus (HIV) infection? With regard to NCI’s finally getting its act together, my perception is that the AIDS community is pleased that there has been a change in leadership at the NCI. The previous era gave us zidovudine (AZT) and didanosine, but unfortunately little was done when it came to AIDS-related cancers. Many of us have wondered why the NCI—with its 250 million dollars in AIDS research funds—is doing so little extramurally to address these cancers. There are some in the AIDS community who trace this failure to the division of labor among the various institutes of the National Institutes of Health (NIH) regarding AIDS. More recently, the NCI should be praised for spearheading new research initiatives on AIDS-related cancers. The NCI recently formed the AIDS Malignancy Consortium (AMC), a clinical trials network that concentrates solely on AIDS-related cancers. In its first year of operation, the AMC already has five studies open to treat either Kaposi’s sarcoma or non-Hodgkin’s lymphoma; two of these studies use conventional chemotherapy together with protease inhibitors, and three studies are employing cytokine inhibitors or immune modulators. The vast majority of the AMC members came directly from the AIDS Clinical Trials Group’s (ACTG) Oncology Committee, whose clinical trials in the late 1980s and early 1990s helped develop a clinical standard of care for Kaposi’s sarcoma and non-Hodgkin’s lymphoma. During that period, we knew very little about the pathogenesis of Kaposi’s sarcoma and nonHodgkin’s lymphoma, and it was up to these researchers to determine the proper therapeutic doses of the limited chemotherapeutic agents that we knew had activity. Thus, these clinical trials taught us how to care properly for people with AIDS who were diagnosed as having Kaposi’s sarcoma and non-Hodgkin’s lymphoma with a scant arsenal of drugs. The ACTG Oncology Committee was, however, working within a clinical trials network filled with infectious disease specialists who had limited expertise in or commitment to AIDS-related cancer clinical research. The oncologists, who used less than 10% of the ACTG’s financial resources, were relegated to a lesser role. Now that the AMC is in its second year, we should ensure its success by providing it with the resources that it needs. The first resource is, of course, money. Increased funding will help laboratory intensive studies that will measure cytokine levels as well as patient’s HIV RNA. The second resource is patients for its studies. For large phase II and phase III studies that are generated from the AMC or the Eastern Cooperative Oncology Group’s AIDS Committee, we will need a majority of the cooperative oncology groups to sponsor these protocols. If this does not work, we might have to return to ACTG for patients. With regard to advisory panels, the NCI needs to use the members of its AIDS Malignancy Working Group (AMWG) more actively. Many from the AMWG helped organize the excellent (and badly needed) National AIDS Malignancy Conference at the NIH, but putting on a conference is not enough. The NCI should form a working group to discuss and formulate AIDS-related cancer RFAs (i.e., requests for application). Yes, there are some legal matters to consider, since some of these experts in the working group would themselves apply, but we should try to work around this situation. The NCI cannot successfully develop such programs without the full involvement of AMWG. The AMWG should be more than window dressing. The community’s second concern can be summarized in the following question: How and when are cancers, such as Kaposi’s sarcoma and non-Hodgkin’s lymphoma, going to be cured and prevented? This is a difficult question, especially coming from the AIDS community who, understandably, has never been known for its patience. The cure for these cancers will eventually come from the work completed by many of the researchers who presented papers at the National AIDS Malignancy Conference. We are just beginning to understand the etiology and pathogenesis of Kaposi’s sarcoma and non-Hodgkin’s lymphoma. Basic scientists and clinicians must work together in the old-fashioned ‘‘bench-to-clinic’’ mode. When trying to turn their discoveries into active agents, basic scientists must use clinicians as consultants. For example, there is still much to learn about Kaposi’s sarcoma herpesvirus (KSHV). We must first answer three integral