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Activity of Thalidomide in AIDS-Related Kaposi’s Sarcoma

From the HIV and AIDS Malignancy Branch, Medicine Branch, and Biostatistics and Data Management Section, Division of Clinical Sciences; Division of Cancer Treatment and Diagnosis; Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute; Division of Hematologic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda; Science Applications International Corporation, Frederick, MD.

Address reprint requests to Robert Yarchoan, MD, Building 10, Room 12N226, M.S.C. 1906, 10 Center Dr, Bethesda, MD 20892-1906; email yarchoan{at}helix.nih.gov

PURPOSE: To assess the toxicity and activity of oral thalidomide in Kaposi’s sarcoma (KS) in a phase II dose-escalation study.

PATIENTS AND METHODS: Human immunodeficiency virus (HIV)–seropositive patients with biopsy-confirmed KS that progressed over the 2 months before enrollment received an initial dose of 200 mg/d of oral thalidomide in a phase II study. The dose was increased to a maximum of 1,000 mg/d for up to 1 year. Anti-HIV therapy was maintained during the study period. Toxicity, tumor response, immunologic and angiogenic factors, and virologic parameters were assessed.

RESULTS: Twenty patients aged 29 to 49 years with a median CD4 count of 246 cells/mm³ (range, 14 to 646 cells/mm³) were enrolled. All patients were assessable for toxicity, and 17 for response. Drowsiness in nine and depression in seven patients were the most frequent toxicities observed. Eight (47%; 95% confidence interval [CI], 23% to 72%) of the 17 assessable patients achieved a partial response, and an additional two patients had stable disease. Based on all 20 patients treated, the response rate was 40% (95% CI, 19% to 64%). The median thalidomide dose at the time of response was 500 mg/d (range, 400 to 1,000 mg/d). The median duration of drug treatment was 6.3 months, and the median time to progression was 7.3 months.

CONCLUSION: Oral thalidomide was tolerated in this population at doses up to 1,000 mg/d for as long as 12 months and was found to induce clinically meaningful anti-KS responses in a sizable subset of the patients. Additional studies of this agent in KS are warranted.

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