Little Richard F, Pluda James M, Wyvill Kathleen M, Rodriguez-Chavez Isaac R, Tosato Giovanna, Catanzaro Andrew T, Steinberg Seth M, Yarchoan Robert
HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1868, USA.
Blood. 2006 Jun 15;107(12):4650-7. doi: 10.1182/blood-2005-11-4455. Epub 2006 Feb 28.
Interleukin-12 (IL-12) enhances Th1-type T-cell responses and exerts antiangiogenic effects. We initiated a phase 1 pilot study of IL-12 in 32 patients with acquired immunodeficiency syndrome (AIDS)-related Kaposi sarcoma (KS) whose KS was progressing while on antiretroviral therapy. Fifteen patients had poor prognosis T(1)S(1) disease. IL-12 was administered subcutaneously twice weekly at doses from 100 to 625 ng/kg. The maximum tolerated dose was 500 ng/kg, and the principal toxicities were flulike symptoms, transaminase or bilirubin elevations, neutropenia, hemolytic anemia, and depression. No tumor responses were seen at the lowest dose (100 ng/kg), but 17 of 24 evaluable patients at the higher doses had partial or complete responses (response rate, 71%; 95% confidence interval, 48%-89%). Only 3 of 17 patients had a change in antiretroviral therapy before responding, and there were no significant differences between responders and nonresponders with regard to changes in CD4 counts or viral loads. Patients had increases in their serum IL-12, interferon-gamma, and inducible protein-10 (IP-10) after the first dose, and increases above baseline persisted after week 4. These results provide preliminary evidence that IL-12 has substantial activity against AIDS-related KS with acceptable toxicity and warrants further investigation for this indication.
白细胞介素-12（IL-12）可增强Th1型T细胞反应并发挥抗血管生成作用。我们对32例获得性免疫缺陷综合征（AIDS）相关卡波西肉瘤（KS）患者开展了一项IL-12的1期初步研究，这些患者在接受抗逆转录病毒治疗时KS仍在进展。15例患者预后较差，属于T(1)S(1)疾病。IL-12每周皮下注射两次，剂量为100至625 ng/kg。最大耐受剂量为500 ng/kg，主要毒性包括流感样症状、转氨酶或胆红素升高、中性粒细胞减少、溶血性贫血和抑郁。最低剂量（100 ng/kg）时未见肿瘤反应，但较高剂量组中24例可评估患者中有17例出现部分或完全反应（反应率为71%；95%置信区间为48%-89%）。17例患者中只有3例在出现反应前改变了抗逆转录病毒治疗，反应者和无反应者在CD4细胞计数或病毒载量变化方面无显著差异。患者在首次给药后血清IL-12、干扰素-γ和诱导蛋白-10（IP-10）升高，且在第4周后仍高于基线水平。这些结果提供了初步证据，表明IL-12对AIDS相关KS具有显著活性，毒性可接受，值得针对该适应证进一步研究。
