Activity of thalidomide in AIDS-related Kaposis's sarcoma
Activity of thalidomide in AIDS-related Kaposis's sarcoma
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DOI：
10.1200/jco.2000.18.13.2593
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发表时间：
2000-07-01
影响因子：
45.3
通讯作者：
Yarchoan, R
中科院分区：
文献类型：
--
作者：
Little, RF;Wyvill, KM;Yarchoan, R
目的：在II期剂量递增研究中评估口服沙利度胺治疗卡波西肉瘤(KS)的毒性和活性。患者和方法：在II期研究中，人类免疫缺陷病毒(HIV)血清阳性患者在登记前2个月内进展，口服沙利度胺200 mg/d。剂量增加到最高1,000毫克/天，最长达1年。在研究期间维持抗艾滋病毒治疗。结果：20例患者年龄29~49岁，CD4中位数为246个/mm(3)(14~646个/mm(3))，所有患者均可评价毒性，其中17例出现反应，9例出现嗜睡，7例出现抑郁。在17例可评估患者中，8例(47%，95%可信区间[CI]，23%~72%)部分缓解，另外2例病情稳定，根据治疗的20例患者，有效率为40%(95%CI，19%对)。反应时沙利度胺的中位剂量为500 mg/d(范围为400~1000 mg/d)。药物治疗的中位持续时间为6.3个月，中位进展时间为7.3个月。结论：口服沙利度胺1000 mg/d在该人群中耐受时间长达12个月，并在相当一部分患者中发现诱导有临床意义的抗KS反应。对这种药物在KS中的进一步研究是有必要的。
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/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 wets 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.