PHASE-I STUDY OF HUMAN CHORIONIC-GONADOTROPIN GIVEN SUBCUTANEOUSLY TOPATIENTS WITH ACQUIRED IMMUNODEFICIENCY SYNDROME-RELATED MUCOCUTANEOUS KAPOSIS-SARCOMA

Background: In vitro and in vivo clinical studies have shown that cert ain preparations of human chorionic gonadotropin have antitumor activi ty against Kaposi's sarcoma, the most common tumor in patients infecte d with human immunodeficiency virus type 1 (HIV-1). Methods: A phase I trial was conducted in 18 male patients with acquired immunodeficienc y syndrome-related Kaposi's sarcoma, Successive cohorts of six patient s each received human chorionic gonadotropin (A.P.L.; Wyeth-Ayerst, Ra dnor, PA) subcutaneously at doses of 5000 IU daily (level I), 10000 IU three times a week (level II), or 10 000 IU daily (level III), Toxic effects, changes in reproductive hormone levels, HIV-1 RNA plasma leve ls, and response to therapy were evaluated, Results: A.P.L. treatment was well tolerated at all dose levels, and no maximum-tolerated, dose- defined toxic effects were observed at the highest dose tested, The mo st common side effects were weight gain, increased libido, and increas ed energy, A persistent increase in testosterone level and a persisten t decline in luteinizing hormone and follicle-stimulating hormone leve ls were seen over time, Major responses were observed in six patients, Partial remissions (greater than or equal to 50% decrease in lesion n umbers, volume, or surface area) were observed at dose level I and dos e level II (two patients each); biopsy-confirmed complete remissions ( resolution of all lesions) were observed at dose level III (two patien ts), All but one major response have persisted from 207 to more than 5 15 days, Nine patients had stable disease lasting 10 weeks or longer, Conclusions: A.P.L. given at daily doses ranging from 5000 to 10000 IU has antitumor activity in patients with acquired immunodeficiency syn drome-related Kaposi's sarcoma, A.P.L. can be given for more than 1 ye ar with minimal side effects, Larger efficacy studies are warranted.