A PHASE II STUDY OF THALIDOMIDE FOR KAPOSI'S SARCOMA

Abstract

BACKGROUND: Thalidomide may have three possible mechanisms of action against Kaposi's sarcoma (KS). It is a selective inhibitor of synthesis of TNFα (an autocrine growth factor in KS), has anti-angiogenic activity in vivo and reduces HIV-1 activation in peripheral blood mononuclear cells (PBMC) in vitro. There is one case report of activity of thalidomide in AIDS KS (Soler et al., 1996). The detection of KSHV (Kaposi's sarcoma herpes virus) in the PBMCs of HIV-seropositive patients by polymerase chain reaction (PCR) has been shown to correlate with the presence of KS and to predict for its development. METHODS: A single institution open label phase II study was designed to establish the activity and toxicity of thalidomide in the treatment of AIDS KS. KSHV DNA levels in PBMCs were determined by PCR quantification and correlated with clinical response. Response evaluation was performed using the AIDS Clinical Trials Group (ACTG) criteria. Only male patients were eligible in view of the teratogenicity of thalidomide. The treatment schedule was thalidomide 100mg orally once at night for an initial study period of two months. RESULTS: Seventeen patients median age 40 years (range 30-48) were enrolled and 11 are evaluable for response. The median CD4 cell count was 36 cells/µl(range 4-552) and 8/17 had prior AIDS defining opportunistic infections. Four patients developed a rash and one Raynaud's syndrome. Six patients were unevaluable due to early withdrawal (toxicity in four patients, progressive disease in one and poor compliance in one). Five of the 11 evaluable patients achieved a partial response. Thus the overall response rate is 45% (95% confidence interval 10-81%). A further two patients had stable disease (18%: 95% confidence interval 0-45%). Results of the PCR quantification for KSHV DNA will be presented. CONCLUSIONS: Although the number of patients in this study is small and therefore the confidence intervals wide, thalidomide appears to have activity in the treatment of AIDS related KS and deserves further investigation. Reference: Soler R, Howard M, Brink N, Gibb D, Tedder R & Nadal D. Regression of AIDS-related Kaposi's sarcoma during therapy with thalidomide. Clin. Infect. Dis 1996:23, 501-503. Acknowledgement: MB and KF are supported by a grant from the Crusaid and Star Foundation.