Ireland Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
J Acquir Immune Defic Syndr. 2011 Jan 1;56(1):64-8. doi: 10.1097/QAI.0b013e3181fc0141.
Using a novel blinded intrapatient vehicle control design, we conducted a phase II study of topically administered halofuginone, an angiogenesis inhibitor that inhibits collagen type-I and matrix metalloproteinases (MMPs), in patients with AIDS-related Kaposi sarcoma. Serial Kaposi sarcoma biopsies assessed treatment effects on angiogenic factors and Kaposi sarcoma herpesvirus-latency associated nuclear antigen-1 (KSHV-LANA). We observed marked heterogeneity of KSHV-LANA expression. Although the small number of subjects whose response could be evaluated precluded definitive assessment of halofuginone's efficacy, we observed a significant decrease in type-I collagen only in halofuginone-treated lesions, but no effect on MMP-2. The trial design is applicable to future studies of topical agents.
采用新型盲法患者自身对照设计,我们开展了一项局部给予海夫定的 II 期研究,海夫定为血管生成抑制剂,可抑制 I 型胶原和基质金属蛋白酶(MMPs)。该研究入组了 AIDS 相关性卡波西肉瘤患者。对卡波西肉瘤活检标本进行连续检测,以评估血管生成因子和卡波西肉瘤疱疹病毒潜伏相关核抗原-1(KSHV-LANA)的治疗效果。我们观察到 KSHV-LANA 表达存在明显异质性。尽管可评估应答的受试者数量较少,无法明确评估海夫定的疗效,但我们仅观察到海夫定治疗病灶中 I 型胶原显著减少,但对 MMP-2 无影响。该试验设计适用于未来的局部药物研究。