Activity of thalidomide in AIDS-related Kaposi's sarcoma

NCI-Frederick, Фредерик, Maryland, United States
Journal of Clinical Oncology (Impact Factor: 18.43). 08/2000; 18(13):2593-602.
Source: PubMed


To assess the toxicity and activity of oral thalidomide in Kaposi's sarcoma (KS) in a phase II dose-escalation study.
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.
Twenty patients aged 29 to 49 years with a median CD4 count of 246 cells/mm(3) (range, 14 to 646 cells/mm(3)) 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.
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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    • "In addition to its antiangiogenic effect, an immunomodulatory function is also a potential mechanism of the anticancer activity of thalidomide. To date, the effectiveness of thalidomide for treating neoplastic disorders has been confirmed in diseases such as multiple myeloma (11) and Kaposi’s sarcoma (12). In addition, thalidomide has been tentatively used for the treatment of advanced hepatocellular carcinoma (13–16). "
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    • "In our cohort, complete regression of lymph nodes and symptoms was observed in 91% of patients and was maintained after discontinuation of treatment with a 2-year PFS of 60% after a median followup of almost 2 years, comparing favourably with rituximab alone (Gerard et al, 2007; Bower et al, 2011). Despite small numbers, the low risk of KS reactivation could be thalidomide-related , as has been previously reported (Little et al, 2000). The duration of maintenance with thalidomide in MCD patients following rituximab-thalidomide combination therapy should be explored in a prospective trial. "

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    • "While the enantiomers can interconvert (racemize) in vivo [86], their pathogenic mechanisms are still not understood. Recently, thalidomide has been considered as a potential drug for various diseases such as autoimmune diseases, AIDS, Hansen’s disease, and some cancers [87, 88]. "
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