AIDS-related Kaposi's sarcoma patients with visceral manifestations. Response to human chorionic gonadotropin preparations.

OBJECTIVE: In vitro cell culture studies and a murine model for human Kaposi's sarcoma (KS) have shown that human chorionic gonadotropin (hCG)-associated factor (HAF) isolated from commercial hCG preparations has antiproliferative and cell killing effects on neoplastic KS cells, without toxic effects on normal endothelial cells and lymphocytes. These findings prompted preliminary study of hCG preparations for patients with early-stage KS with skin lesions only and no known visceral involvement. Complete or partial regression of the skin lesions occurred after intralesional injections of hCG (hCG-Pregnyl, hCG-APL). The current study sought to extend these early observations to evaluation of the safety of hCG in acquired immunodeficiency syndrome (AIDS) KS patients with aggressive disease and visceral involvement. These patients present in a more advanced stage of the disease that is coupled with serious immunodeficiency. They commonly respond poorly to conventional chemotherapy and have a reduced median life expectancy of only 4 to 9 months.

STUDY DESIGN/METHODS: After approval by the local institutional review boards, 13 patients with advanced AIDS-KS gave informed consent and were treated with hCG preparations. These hCG preparations are known to have antiproliferative activity in laboratory tests. Patients were monitored for tumor size by clinical evaluation, ultrasonography, radiography, respiratory functions, and endoscopic examination. Histologic examinations of biopsied tissues were used for studies of apoptosis using in situ hybridization techniques. The patients were also monitored for CD4+ T-cell numbers and human immunodeficiency virus type 1 (HIV-1) plasma viral load according to common clinical practice.

RESULTS: Thirteen patients with advanced AIDS-KS and visceral KS were treated with hCG. Five of 13 (38%) patients had dramatic responses to therapy, and overall tolerance to the drug was excellent for all patients. Some hCG preparations also showed beneficial effects against HIV-associated markers. An accompanying decrease in viral load (plasma HIV-1 RNA) was observed in one patient, a dramatic increase in CD4+ cells occurred in another, and significant weight gain was seen in seven patients.

CONCLUSIONS: These clinical observations suggest that patients with aggressive visceral forms of KS, usually indicative of an extremely poor prognosis and poor response to combined chemotherapy, can benefit from this new therapeutic approach. In some patients, these preparations also induce several other beneficial effects, such as weight gain, reduction in HIV-1 RNA load, or increase in the CD4+ T-cell count. Additional controlled clinical trials comparing this new therapeutic option with standard cytotoxic chemotherapy are needed. These trials should be extended to patients with KS not related to HIV-1 infection. Because we showed elsewhere that pure hCG had no effect on KS, identification and subsequent clinical use of the active molecules in hCG preparations is urgently needed.