论文部分内容阅读
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 PEG-rhG-CSF injected by Beijing Shuanglu Pharmaceutical Co., Ltd. in the prevention of chemotherapy-induced neutropenia. Its effect of raising peripheral blood neutrophil and CD3 + 4 cells, to explore the dose-effect relationship, and through human pharmacokinetic test understanding of the drug absorption, distribution and elimination in the human body, for the development of Phase II clinical study Dosing program to provide the basis. Methods: As an open-label test, all subjects were newly-treated patients with malignant tumor. The patients were treated with two cycles of paclitaxel plus carboplatin for one week. The first cycle was the control cycle. The second cycle of chemotherapy was administered 48 hours after the end of the administration of PEG -rhG-CSF; the initial dose was 30μg.kg-1, and the increasing doses were 60, 100, 150 and 200μg.kg-1. Results: A total of 34 patients were included in the study. Thirty patients were evaluated for efficacy and safety. Adverse reactions associated with PEG-rhG-CSF Only muscular joint pain (8/30) in the trunk and limbs of I to II degrees was observed. Compared with the control period, the PEG-rhG-CSF cycle was used to reduce the incidence of IV neutrophil absolute (ANC) reduction during chemotherapy, and the ANC showed a bimodal change with the time of study. The lowest ANC in peripheral blood Shift, and significantly increased; the lowest value and the second peak changes, showing a certain amount of dose-effect relationship. CONCLUSIONS: PEG-rhG-CSF demonstrated good tolerability in this study with no dose-limiting toxic dose nor the maximum tolerated dose. In view of its efficacy has met clinical needs, recommended PEG-rhG-CSF Phase II clinical trials of the dose of 60 and 100μg.kg-1.