Interferon-α2b with protease inhibitor-based antiretroviral therapy in patients with AIDS-associated Kaposi sarcoma -: An AIDS malignancy consortium phase I trial
Interferon-α2b with protease inhibitor-based antiretroviral therapy in patients with AIDS-associated Kaposi sarcoma -: An AIDS malignancy consortium phase I trial
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DOI：
10.1097/01.qai.0000194237.15831.23
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发表时间：
2006-02-01
影响因子：
3.6
通讯作者：
Von Roenn, JH
中科院分区：
文献类型：
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作者：
Krown, SE;Lee, JY;Von Roenn, JH
我们在14例艾滋病相关卡波西肉瘤（KS）患者的1期研究中评估了干扰素（IFN）-α 2b联合基于蛋白酶促生长剂的高效抗逆转录病毒治疗（HAART）的安全性和最大耐受剂量。计划的IFN剂量水平为0、1、5、10和1500万IU，每日皮下注射给药。剂量限制性毒性为中性粒细胞减少和不适。IFN最大耐受剂量为500万IU/d。中位CD 4计数从基线时的260个细胞/μ L增加至研究期间的最大值359个细胞/μ L。在6例基线值和研究期间值配对的患者中，中位HIV RNA水平从20，179拷贝/mL降至最低研究期间值309拷贝/mL。在13例KS缓解可评价的患者中，5例显示客观肿瘤消退。在HAART经验和HAART初治受试者中发生应答。5名患者，包括2名应答者，2名稳定KS，1名进展，进行了卡波西肉瘤疱疹病毒（KSHV）载量的系列测量。无论治疗组或KS应答如何，这些患者均未显示KSHV从血浆或外周血单核细胞中持久清除。这项研究建立了一个安全剂量的干扰素，可用于HAART，并可能与其他抑制剂的KS在未来的临床试验。
We evaluated the safety and maximum tolerated dose of interferon (IFN)-alpha 2b in combination with protease inhibitor-based highly active antiretroviral therapy (HAART) in a phase 1 study in 14 patients with AIDS-associated Kaposi sarcoma (KS). Planned IFN dose levels were 0, 1, 5, 10, and 15 million IU administered by daily subcutaneous injection. Dose-limiting toxicities were neutropenia and malaise. The maximum tolerated IFN dose was 5 million IU/d. The median CD4 count increased from 260 cells/mu L at baseline to a maximum on-study value of 359 cells/mu L. In 6 patients with paired baseline and on-study values, the median HIV RNA level decreased from 20,179 copies/mL to a minimum on-study value of 309 copies/mL. Of 13 patients whose KS response could be evaluated, 5 showed objective tumor regression. Responses occurred in HAART-experienced and HAART-naive subjects. Five patients, including 2 responders, 2 with stable KS, and 1 with progression, had serial measurements of Kaposi sarcoma herpesvirus (KSHV) load. None of these patients, irrespective of treatment arm or KS response, showed durable clearance of KSHV from plasma or peripheral blood mononuclear cells. This study establishes a safe dose of IFN that can be used with HAART and, potentially, with other inhibitors of KS in future clinical trials.