AIDS-related Kaposi's Sarcoma: Options for Today and Tomorrow

Prior to 1981, Kaposi sarcoma (KS) was considered a rare human cancer occurring primarily among elderly Italian and Jewish men of eastern European ancestry. I wrote a review of KS research and clinical experiences that appeared in CA: A Cancer Journal for Clinicians. Publication of this article in January 1981 coincided with a dramatic upsurge in the number of cases of KS in young homosexual males reported to the Centers for Disease Control. The general lack of information about this disease was readily apparent when, upon publication of this article, my office was inundated with calls from physicians requesting additional information on this disease. Later on it was recognized that KS among young homosexual men was actually part of the clinical syndrome seen in the epidemic of acquired immune deficiency syndrome (AIDS).

The body of clinical experience with AIDS-related KS has grown significantly over the past 15 years. This experience has led to a greater understanding of the pathogenesis of KS in general, and angiogenesis and tumor growth factors in particular, and to the establishment of protocols for treating patients with AIDS-related KS. Now, physicians can usually diagnose this disease on a clinical basis, and pathologists can diagnose it with certainty on histologic grounds.

The purpose of this symposium was to review our experience with KS in patients with AIDS and to provide an update on KS epidemiology, pathology, and clinical presentation in AIDS patients. Current treatment options were discussed, as well as treatment modalities that are expected to be available in the near future.

The Epidemiologic Scope of Kaposi's Sarcoma

Worldwide, there are four clinical presentations of KS--the classic form, the African form, the form observed in transplant patients who are immunocompromised as a result of immunosuppressive drug therapy, and the AIDS form. Dr. Haverkos discusses in detail differences in the epidemiology and clinical presentation of these four forms of KS. Data suggest that the cause of AIDS-related KS is multifactorial. In addition to HIV infection, it has been hypothesized that necessary or enhancing cofactors associated with the development of this form of KS may include a genetic predisposition, the use of nitrite inhalants, a second sexually transmitted agent, or a fecal/oral agent. Dr. Haverkos supports this hypothesis using comprehensive epidemiologic data from the Centers for Disease Control and his own extensive research.

Clinical Manifestations of Kaposi's Sarcoma

In my presentation I discuss the clinical manifestations of KS. We have proposed that the etiologic factor responsible for KS is immune dysregulation, rather than immune deficiency. Epidemiologic data further suggest that the homosexual life-style contributes to conditions necessary for the development of this form of KS. The sexually transmissible cytomegalovirus and human papillomaviruses have been implicated in particular. Also implicated are the potentially mutagenic drugs, such as nitrite inhalants, that are frequently abused by AIDS patients prior to their becoming ill.

Current Theraputic Regimens for Karposi's Sarcoma

Treatment options available to patients with AIDS-related KS have not advanced significantly over the past decade. Radiation therapy, chemotherapy, and the use of biologic response modifiers continue as the standard treatment modalities. The efficacy of these treatment options is expertly reviewed by Dr. Abrams, who also discusses strategies for ameliorating potential side effects associated with them. Also discussed are promising new drugs, including inhibitors of viral proteins and antiangiogenesis agents, which, when coupled with new drug delivery systems, may more effectively target KS lesions and thus lessen dose-limiting side effects.

Current Studies on the Use of Liposomal Daunorubicin in Karposi's Sarcoma

Dr. Chew continues with a discussion of the pharmacokinetics of agents used in the treatment of AIDS-related KS accompanied by cutaneous disease with nodular lesions. In addition to disfigurement and skin ulcerations, extensive cutaneous disease can cause serious morbidity. More than 50% of patients with KS have oral cavity or gastrointestinal tract involvement that may lead to gastrointestinal hemorrhage; pulmonary involvement is not uncommon. Clinical studies suggest that the liposomal formulation of daunorubicin is an effective palliative agent for these patients and is associated with minimal toxicity. Encapsulation of daunorubicin also allows for targeting delivery of the drug to tumor cells without destroying surrounding tissue. Although not curative for KS, it has produced a response rate of 67% and the duration of these responses averages more than 100 days.

New Developments: A Look to the Future

Studies of the pathogenesis of KS contribute to a broader understanding of tumor biology in general and angiogenesis in particular. Dr. Gallo discusses studies that strongly suggest that the triggering mechanisms responsible for the development of early KS in HIV-related forms of the disease are the release of Tat from acutely infected T-cells and HIV-associated dysfunction in immune regulation, leading to an increase in inflammatory cytokine levels. Dr. Gallo also explains how activated spindle cells appear to provide a self-perpetuating, autocrine-supported mechanism for further development of the hyperplastic lesions and, in more advanced stages, neoplasms associated with KS.