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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 non-Hodgkin'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 questions: 1) Is KSHV a true cause of Kaposi's sarcoma or just a helper virus? 2) What are the roles of cytokines and growth factors? 3) Which assay is most sensitive, and how soon can we start using these assays for screening patients? In our quest for these cures, industry—especially the biotech companies—will need to take a more active role in AIDS-related cancer clinical research. They must provide their agents to knowledgeable AIDS oncologists for pilot studies or to the NCI for use in the AMC or cooperative oncology group studies. The U.S. Food and Drug Administration (FDA) must also get more involved. Its Oncologic Drug Division needs to fully understand all aspects of AIDS-related Kaposi's sarcoma and AIDS-related non-Hodgkin's lymphoma. While it should ensure that industry carries out safe and well-designed clinical trials, the Oncologic Drug Division must realize that AIDS-related Kaposi's sarcoma not only causes morbidity and mortality but also emotionally damages patients with AIDS. The Oncologic Drug Division should ensure that the Oncologic Drug Advisory Committee has at least three reviewers who are knowledgeable in all aspects of AIDS-related cancers when AIDS-related Kaposi's sarcoma and AIDS-related non-Hodgkin's lymphoma new drug applications (NDAs) are reviewed. Likewise, the Oncologic Drug Division should attempt to work closely with the Antiviral Drug Division when it is reviewing AIDS-related Kaposi's sarcoma and AIDS-related non-Hodgkin's lymphoma NDAs. The FDA and the NCI should be applauded for working together on developing clinical end points for Kaposi's sarcoma that will be used alongside classic tumor response. The use of these newly developed clinical end points, such as pain, skin lesion color, and edema, will help us evaluate the true effectiveness of experimental agents. To test new agents and possibly use these new end points, we will need patients for these studies. Accrual for studies on AIDS-related cancer, like that for most cancer studies, is abysmal. One solution to this problem might be to form close ties with primary care physicians and AIDS clinicians at hospitals and clinic sites so that patients with Kaposi's sarcoma and non-Hodgkin's lymphoma are routinely referred to AIDS oncologists and are informed of studies that have opened. The final concern of the AIDS community is a frequently asked question: How can we be sure that we will receive the best medical care for these cancers and the underlying HIV infection? To ensure that patients receive the best medical care for their cancers, we must attempt to adopt standard (and evolving) practices and principles of the therapy. As stated earlier, clinical trials that were completed in the last 10 years helped us to understand what drugs (and at what doses) were best for patients with disease at various stages. We know how to use radiation, interferon, ABV (i.e., doxorubicin-bleomycin-vinblastine), liposomal doxorubicin, liposomal daunorubicin, and paclitaxel to treat Kaposi's sarcoma, and we know that modified doses of doxorubicin hydrochloride and cyclophosphamide are warranted for the severely immunocompromised patients with AIDS-related non-Hodgkin's lymphoma. Although convening a government panel to draft practices and principles of therapy for AIDS-related Kaposi's sarcoma was suggested to the NCI at its AMWG meeting in September 1996, no action has yet been taken on this recommendation. My sense is that many in the AIDS community believe that this lack of action represents an abdication of the government's public health responsibility. The U.S. Public Health Service convened two panels that recently published guidelines for anti-HIV therapy and treatment for opportunistic infections. Even though the field is still evolving in these areas, the guidelines will ensure that patients receive the best up-to-date AIDS clinical care. Nevertheless, a Kaposi's sarcoma practices and principles of therapy panel was convened. However, it was sponsored by a small biotech company that took the idea and ran with it. Granted, this company has a financial interest in the outcome of these recommendations, but it was able to assemble an excellent panel of experienced AIDS oncologists, an AIDS clinician, a dermatologist, and an radiation oncologist to discuss methods of treatment of patients with various clinical presentations of Kaposi's sarcoma. The recommendations that will come from this panel will not hold as much weight as ones that should come from the NCI. It is necessary to give certain guidelines to all those who treat patients with Kaposi's sarcoma. To instruct a physician about when it is time to use systemic therapy with either interferon or cytotoxic chemotherapy and when it is no longer appropriate to use cryotherapy or intralesional vinblastine will undoubtedly help patients. Until the NCI decides that this a worthwhile initiative, they should see to it that the new Public Health Service guidelines for HIV therapy and opportunistic infection treatment and prophylaxis get into the hands of as many oncologists as possible. For the treatment of patients with Kaposi's sarcoma, non-Hodgkin's lymphoma, or anal or cervical dysplasia, the underlying HIV infection must always be taken into account and treated properly. The AIDS community is anxious to see new developments in AIDS-related cancer research. Now that people with AIDS are living longer with the advent of protease inhibitors in combination with nucleoside analogues, it is certain that the rates of AIDS-related Kaposi's sarcoma and non-Hodgkin's lymphoma will increase. Thus, clinical and basic AIDS-related cancer research needs to be of concern for all those working in AIDS. Oxford University Press Oxford University Press
JNCI Monographs – Oxford University Press
Published: Apr 1, 1998
Keywords: cancer; immunologic deficiency syndromes; kaposi sarcoma; acquired immunodeficiency syndrome; community; national cancer institute; aids-related malignancies
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