注射用聚乙二醇化重组人粒细胞集落刺激因子I期临床耐受性试验  

Phase Ⅰ Clinical Trail of Intravenous Pegylated Recombinant Human Granulocyte Colony-stimulating Factor

作　　者：石远凯[1] 刘鹏[1] 杨晟[1] 韩晓红[1] 何小慧[1] 艾斌[1] 秦燕[1] 李博[1] 黄鼎智[1] 张长弓[1] 孙燕[1] 

机构地区：[1]中国医学科学院中国协和医科大学肿瘤医院/肿瘤研究所内科,北京100021

出　　处：《癌症》2006年第4期495-500,共6页Chinese Journal of Cancer

摘　　要：背景与目的:重组人粒细胞集落刺激因子(rhG-CSF)是防治肿瘤化放疗引起的中性粒细胞减少症的有效药物,但半衰期短,需每日给药。聚乙二醇化重组人粒细胞集落刺激因子(PEG-rhG-CSF)是将聚乙二醇与rhG-CSF结合而成的长效制剂,与常规rhG-CSF相比,能减少给药次数,避免患者反复接受注射的痛苦。本研究旨在评价PEG-rhG-CSF用于国人的安全性和耐受性,初步观察化疗后PEG-rhG-CSF升高外周血中性粒细胞和CD34+细胞的效果。方法:本研究为开放性试验,经病理组织学或细胞学确诊的初治非小细胞肺癌和乳腺癌患者进入本研究,受试者接受两个周期相同方案的化疗,第一周期为对照周期,第二周期在化疗药物给药结束后48h给予PEG-rhG-CSF。PEG-rhG-CSF的初始剂量为30#g/kg,递增剂量依次为60#g/kg、100#g/kg和200#g/kg,每一剂量组4例受试患者。结果:入组16例患者均可评价疗效和安全性。与PEG-rhG-CSF相关的不良反应主要有骨关节或肌肉疼痛(13/16)、疲乏(10/16)、头晕(2/16),1例受试患者出现注射部位轻度疼痛,自行缓解。与对照周期相比,使用PEG-rhG-CSF后中性粒细胞绝对值(ANC)最低值的出现时间前移,ANC最低值提高。ANC的变化呈现一定程度的量效关系,60、100和200#g/kg剂量组均能较好地防治化疗后的中性粒细胞减少症,且维持时间较长,并能够增高外周血CD34+细胞的数量。未出现PEG-rhG-CSF的剂量限制性毒性,也未达到最大耐受剂量。结论:PEG-rhG-CSF显示了良好的耐受性,未出现严重不良事件。由于100#g/kg剂量组的不良反应轻于200#g/kg剂量组,疗效已能满足临床需要,因此推荐Ⅱ期临床试验的剂量为100#g/kg。BACKGROUND ＆ OBJECTIVE： Recombinant human granulocyte colony-stimulating factor （rhG-CSF） is effective in the prophylaxis and management of chemotherapy-induced neutropenia, but requires daily administration because of its short half-life. Pegylated rhG-CSF （PEG-rhG-CSF） is a long-acting reagent that permits less frequent injection. This study was to evaluate the safety and tolerance of PEG-rhG-CSF in Chinese patients, and to explore its efficacy of enhancing absolute neutrophil count （ANC） and CD34^＋ cell count in peripheral blood. METHODS： Naive nonsmall lung cancer or breast cancer patients with normal bone marrow function were eligible for this open-labeled, dose-escalation trial. All patients received 2 cycles of chemotherapy of identical regimen. In cycle 1, rhG-CSF （150μg/ day） was administrated in case of febrile neutropenia or grade 4 neutropenia;in cycle 2, patients received a single injection of PEG-rhG-CSF （30μg/kg, 60μg/kg, 100μg/kg, or 200 μg/kg） 48 h after administration of paclitaxel and carboplatin. RESULTS. All the 16 patients enrolled （4 in each dose group） were evaluable for safety and efficacy of PEG-rhG-CSF. Main adverse events related to PEG-rhG-CSF were musculoskeletal pain or arthralgia （13/ 16）, fatigue （10/16）, dizziness （2/16）, and injection-site pain （1/16）. All adverse events were mild to moderate, and most of them were reversible without treatment. PEG-rhG-CSF enhanced ANC in a dose-dependent manner to some extent, and PEG-rhG-CSF at 60μg/kg or higher doses preventedchemotherapy-induced neutropenia with sustained effect; CD34^＋ cells in peripheral blood were also increased. CONCLUSIONS; PEG-rhG-CSF is well tolerated, with no serious adverse event in this trial. The recommended dose of PEG-rhG-CSF for phase Ⅱ trial is 100μg/kg because of its adequate efficacy and less adverse events than those of 200 μg/kg.

关 键 词：肿瘤 聚乙二醇化 粒细胞集落刺激因子 临床试 验 Ⅰ期 药物耐受性 

分 类 号：R730.5[医药卫生—肿瘤]