注射用聚乙二醇化重组人粒细胞集落刺激因子Ⅰ期临床试验  

Phase I clinical trail of intravenous pegylated recombinant human granulocyte colony-stimulating factor

作　　者：刘鹏[1] 石远凯[1] 杨晟[1] 秦燕[1] 杨建良[1] 董梅[1] 张淑香[1] 张敬 杨彩霞 

机构地区：[1]中国医学科学院北京协和医学院肿瘤医院肿瘤研究所,北京100021 [2]北京双鹭药业股份有限公司,北京100037

出　　处：《中国新药杂志》2012年第8期895-898,共4页Chinese Journal of New Drugs

基　　金：国家“重大新药创制”科技重大专项(2008ZX09312-02;2011ZX09101-001-13)

摘　　要：目的:评价北京双鹭药业股份有限公司研制的注射用聚乙二醇化重组人粒细胞集落刺激因子(PEG-rhG-CSF)用于预防化疗引起的中性粒细胞减少症的安全性,观察其升高外周血中性粒细胞和CD3+4细胞的效果,探讨量效关系,并通过人体药代动力学试验了解该药在人体内的吸收、分布和消除规律,为制定II期临床研究给药方案提供依据。方法:作为开放性试验,受试者均为初治的恶性肿瘤患者,连续接受两个周期紫杉醇联合卡铂方案化疗,第1周期为对照周期,第2周期化疗药物给药结束48 h给予PEG-rhG-CSF;其初始剂量为30μg.kg-1,递增剂量依次为60,100,150和200μg.kg-1。结果:共入组34例患者,30例可评价疗效和安全性。与PEG-rhG-CSF相关的不良反应仅观察到I～II度躯干及四肢的肌肉关节痛(8/30)。较之对照周期,应用PEG-rhG-CSF周期,化疗期间IV度中性粒细胞绝对值(ANC)减少症的发生率明显减少,且ANC随研究时间呈双峰改变,外周血ANC最低值前移,并明显提高;其最低值及第二峰的峰值变化,呈一定程度的量效关系。结论:本项研究中PEG-rhG-CSF表现出良好的耐受性,未见到剂量限制性毒性剂量,也未达到最大耐受剂量。鉴于其疗效已满足临床需要,推荐PEG-rhG-CSF II期临床试验研究的用药剂量为60和100μg.kg-1。Objective： To evaluate the safety of Pegylated Recombinant Human Granulocyte Colony-stimulating Factor（PEG-rhG-CSF）,which developed by Beijiing SL Pharmaceutical Co.,Ltd,and to explore its efficacy of enhancing absolute neutrophil count（ANC） and CD＋34 cell count in pripheral blood after chemotherapy,as well as pharmacokinetic data,as the basis for phase II clinical study.Methods： As an open,single-center Phase I trial,untreated patients received sequential two cycles of chemotherapy with paclitaxel and carboplatin.The first cycle of chemotherapy was the control cycle,different groups of patients received a single injection of PEG-rhG-CSF（30,60,100,150 or 200 μg·kg-1） 48 h after administration of the second cycle of chemotherapy.Results： 30 of 34 cases were evaluable for safety and efficacy of PEG-rhG-CSF.Main adverse events related to PEG-rhG-CSF was mild musculoskeletal pain or arthralgia（8/30）.With less severe neutropenia founded after chemotherapy,PEG-rhG-CSF enhanced ANC in a dose-dependent manner to some extent with peripheral nadir ANC to move forward,and significantly improved.Conclusion： PEG-rhG-CSF is well tolerated,neither the dose limiting toxicity（DLT） dose,nor the maximum tolerance dose（MTD） was reached in the trial.The recommended dose of PEG-rhG-CSF for phase II trial is 60 and 100 μg·kg-1,with its adequate efficacy.

关 键 词：肿瘤 化疗 中性粒细胞减少症 聚乙二醇化重组人粒细胞集落刺激因子 I期临床研究 

分 类 号：R969.4[医药卫生—药理学]