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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 总被引:1,自引:0,他引:1
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。 相似文献
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国产重组人粒细胞—巨噬细胞集落刺激因子Ⅰ期临床研究报告 总被引:3,自引:0,他引:3
重组人粒细胞-巨噬细胞集落刺激因子(rhGM-CSF)是通过基因工程方法产生的细胞因子,对肿瘤化疗、放疗引起的粒细胞减少症,继发感染与免疫功能低下具有明显的治疗作用。为考察国产rhGM-CSF的毒性反应及耐受剂量,初步了解治疗白细胞减少的疗效,对13例住院的肿瘤患者进行了国产rhG-M-CSF的Ⅰ期临床试验。试验设置1.25μg/kg、2.5μg/kg、5μg/kg、7.5μg/kg四个剂量组,每例用药7天。共用药91人次,观察到10种不良反应,但均可以耐受。同时初步观察到2.5、5.0、7.5μg/kg三个剂量组都有不同程度的升高白细胞作用。 相似文献
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目的:比较每周期1 剂聚乙二醇化重组人粒细胞集落刺激因子(PEG-rhG-CSF)与每日1 剂重组人粒细胞集落刺激因子(rhG-CSF )预防癌症患者化疗后中性粒细胞减少的有效性。方法:合并分析PEG-rhG-CSF的2 期和3 期临床研究中的单中心数据,比较疗效与安全性指标。两项研究均为随机、自身交叉对照试验。56例初治恶性肿瘤患者接受2 个周期常用化疗方案治疗,且化疗方案相同,其中试验周期给予PEG-rhG-CSF100 μ g/kg 皮下注射,每个周期1 次;对照周期皮下注射rhG-CSF 5 μ g/kg ,
每日1 次。结果:2 个研究单中心共纳入56例患者,其中53例可进行疗效评价,PEG-rhG-CSF和rhG-CSF 各使用53个周期。在使用PEG-rhG-CSF的周期和使用rhG-CSF 的周期中,4 度外周血中性粒细胞绝对值(ANC )减少未发生率均为94.3%(50/ 53),均未出现中性粒细胞减少性发热,抗生素使用率分别为7.5%(4/ 53)和3.8%(2/ 53,P = 0.678)。 全组患者中位应用rhG-CSF 天数为10(3~14)天。此两种药物的不良反应均为骨痛、注射部位疼痛、心悸、发热和乏力等。结论:1 剂聚乙二醇化重组人粒细胞集落刺激因子预防化疗后中性粒细胞减少的有效性与连续10剂常规重组人粒细胞集落刺激因子相似。 相似文献
每日1 次。结果:2 个研究单中心共纳入56例患者,其中53例可进行疗效评价,PEG-rhG-CSF和rhG-CSF 各使用53个周期。在使用PEG-rhG-CSF的周期和使用rhG-CSF 的周期中,4 度外周血中性粒细胞绝对值(ANC )减少未发生率均为94.3%(50/ 53),均未出现中性粒细胞减少性发热,抗生素使用率分别为7.5%(4/ 53)和3.8%(2/ 53,P = 0.678)。 全组患者中位应用rhG-CSF 天数为10(3~14)天。此两种药物的不良反应均为骨痛、注射部位疼痛、心悸、发热和乏力等。结论:1 剂聚乙二醇化重组人粒细胞集落刺激因子预防化疗后中性粒细胞减少的有效性与连续10剂常规重组人粒细胞集落刺激因子相似。 相似文献
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目的:比较聚乙二醇化重组人粒细胞集落刺激因子 (PEG-rhG-CSF) 和重组人粒细胞集落刺激因子 (rhG-CSF) 预防化疗后中性粒细胞减少症的有效性和安全性.方法:采用随机自身交叉对照,选择初治恶性肿瘤患者接受2个周期相同方案的化疗,其中试验周期给予PEG-rhG-CSF 100 μg/kg皮下注射一次,对照周期每日一次皮下注射rhG-CSF 5 μg/kg,直至外周血中性粒细胞绝对值 (ANC) 在低谷后连续两次检查≥5.0×109/L.结果:入组78例患者,在76个试验周期和74个对照周期中,ANC<1.5×109/L的发生率分别为30.26%和21.16%,持续时间分别为2.34 d和2.31 d; ANC<0.5×109/L的发生率分别为3.8%和3.0%; 抗生素使用率分别为11.59%和9.60% (P均<0.05).试验药和对照药的不良反应均为骨骼肌肉疼痛、乏力、发热、头晕等,发生率与严重程度相似.结论:PEG-rhG-CSF一次给药的疗效和不良反应与rhG-CSF多次给药相似. 相似文献
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比较聚乙二醇化重组人粒细胞集落刺激因子(PEG-rhG-CSF)和重组人粒细胞集落刺激因子(rhG-CSF)预防化疗后中性粒细胞减少症的有效性和安全性。方法:采用随机自身交叉对照,选择初治恶性肿瘤患者接受2个周期相同方案的化疗,其中试验周期给予PEG-rhG-CSF 100 μg/kg皮下注射一次,对照周期每日一次皮下注射rhG-CSF 5 μg/kg,直至外周血中性粒细胞绝对值(ANC)在低谷后连续两次检查≥5.0×109/L。结果:入组78例患者,在76个试验周期和74个对照周期中,ANC<1.5×109/L的发生率分别为30.26%和21.16%,持续时间分别为2.34 d和2.31 d;ANC<0.5×109/L的发生率分别为3.8%和3.0%;抗生素使用率分别为11.59%和9.60%(P均<0.05)。试验药和对照药的不良反应均为骨骼肌肉疼痛、乏力、发热、头晕等,发生率与严重程度相似。结论:PEG-rhG-CSF一次给药的疗效和不良反应与rhG-CSF多次给药相似。 相似文献
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国产基因重组人粒细胞集落刺激因子Ⅱ期临床研究报告 总被引:2,自引:0,他引:2
目的对五家单位生产的rbG-CSF进行疗效及毒副作用的Ⅱ期临床研究。方法 观察60例病人,随机分组,采用自身交叉方法。结果 五个rhG-CSF均可明显升高ANC和WBC,升高曲线呈双峰状态,可促进化疗病人WBC和ANC的恢复,缩短WBC和ANC减少的持续时间;对血红蛋白和血小板未见明显影响。主要不良反应有发热、局部反应、感冒样症状、骨肌肉疼痛和皮疹等。五个产品在疗效和不良反应方面无明显差别。结论 相似文献
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《中国肿瘤临床与康复》2016,(1)
目的评价单次给予不同剂量聚乙二醇化重组人粒细胞刺激因子(PEG-rh G-CSF)预防乳腺癌患者化疗后引起的中性粒细胞减少的安全性与疗效。方法按随机、平行分组、开放性、阳性对照原则,将受试者按1∶1∶1∶1比例随机分为PEG-rh G-CSF 60μg/kg组、PEG-rh G-CSF100μg/kg组、PEG-rh G-CSF 120μg/kg组和rh G-CSF 5μg·kg~(-1)·d~(-1)组,所有患者采用TAC化疗方案。化疗21d为1个周期。结果 4度中性粒细胞减少的发生率比较显示,PEG-rh G-CSF 60μg/kg组高于rh G-CSF5μg·kg~(-1)·d~(-1)组,PEG-rh G-CSF 100μg/kg组和PEG-rh G-CSF 120μg/kg组与rh G-CSF 5μg·kg~(-1)·d~(-1)组相当。4度中性粒细胞减少的持续时间比较显示,PEG-rh G-CSF 60μg/kg组长于rh G-CSF5μg·kg~(-1)·d~(-1)组,PEG-rh G-CSF 100μg/kg组和PEG-rh G-CSF 120μg/kg组与rh G-CSF 5μg·kg~(-1)·d~(-1)组相当。PEG-rh G-CSF 60μg/kg组、PEG-rh G-CSF 100μg/kg组和PEG-rh G-CSF 120μg/kg组中性粒细胞减少性发热的发生率分别为7.0%、4.7%和11.9%,rh G-CSF 5μg·kg~(-1)·d~(-1)组为11.6%,差异无统计学意义(P=0.5043)。PEG-rh G-CSF 60μg/kg组、PEG-rh G-CSF 100μg/kg组和PEG-rh G-CSF120μg/kg组从化疗用药结束到中性粒细胞减少达到最低点的时间分别为(7.88±1.80)d、(7.88±2.12)d和(7.14±1.05)d,而rh G-CSF 5μg·kg~(-1)·d~(-1)组为(8.93±3.39)d,差异有统计学意义(P=0.0008)。PEG-rh G-CSF 60μg/kg组、PEG-rh G-CSF 100μg/kg组和PEG-rh G-CSF 120μg/kg组中性粒细胞减少从最低值达2.0×109/L以上所需要的时间分别为(3.44±3.08)d、(2.47±1.79)d和(2.90±2.54)d,rh G-CSF 5μg·kg~(-1)·d~(-1)组为(4.02±4.04)d,差异无统计学意义(P=0.0982)。PEG-rh G-CSF 60μg/kg组、PEG-rh G-CSF 100μg/kg组和PEG-rh G-CSF 120μg/kg组和rh G-CSF5μg·kg~(-1)·d~(-1)组不良事件的发生率分别为95.4%(41/43)、93.0%(40/43)、92.9%(39/42)和90.7%(39/43),差异无统计学意义(P=0.9202)。结论接受TAC化疗方案的乳腺癌患者于化疗后48 h单次注射PEG-rh G-CSF 100μg/kg,不良反应程度轻。单次注射PEG-rh G-CSF 100μg/kg与连续注射rh G-CSF 5μg·kg~(-1)·d~(-1)比较,预防化疗引起的中性粒细胞减少的安全性和疗效相当,推荐以PEG-rh G-CSF 100μg/kg进行Ⅲ期临床试验。 相似文献
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目的探讨聚乙二醇化重组人粒细胞集落刺激因子(PEG-rhG-CSF)用于多发性骨髓瘤(MM)患者外周血造血干细胞动员(PBSCM)的效果及药物经济学价值。方法回顾性分析2015年1月至2017年10月在吉林大学第一医院和中国医学科学院血液病医院住院治疗的91例初治MM患者资料。根据患者意愿,采用大剂量化疗结合皮下注射PEG-rhG-CSF或重组人粒细胞集落刺激因子(rhG-CSF)进行干细胞动员,分别为42、49例。分析两组动员后采集单个核细胞(MNC)数、采集物CD34+细胞数、动员中最高中性粒细胞(mANC)数、动员的费用以及移植后白细胞和血小板植入时间。结果PEG-rhG-CSF组和rhG-CSF组的中位采集MNC数分别为5.86×108/kg[(1.08~24.54)×108/kg]和6.61×108/kg[(0.83~33.80)×108/kg],差异无统计学意义(U=883.00,P=0.245);PEG-rhG-CSF组的中位采集物CD34+细胞数高于rhG-CSF组,分别为5.56×106/kg[(0.94~19.90)×106/kg]和4.82×106/kg[(1.12~14.61)×106/kg],差异有统计学意义(U=732.00,P=0.038)。PEG-rhG-CSF组动员期间中位mANC数较rhG-CSF组低,分别为20.50×109/L[(7.26~61.30)×109/L]和32.08×109/L[(6.92~69.99)×109/L],差异有统计学意义(U=490.00,P=0.001)。自体干细胞移植(ASCT)后,PEG-rhG-CSF组白细胞计数(WBC)恢复至1.0×109/L的时间较rhG-CSF组短[(11.59±1.98)d比(12.93±2.83)d],差异有统计学意义(t=-2.395,P=0.019);PEG-rhG-CSF组血小板计数(Plt)恢复至20.0×109/L的时间也较rhG-CSF组有缩短趋势[(12.86±2.62)d比(14.80±5.47)d],但差异无统计学意义(t=-1.749,P=0.085)。PEG-rhG-CSF组的动员总费用与rhG-CSF组差异无统计学意义[(21405.47±7365.98)元比(22976.83±10264.34)元,t=-0.721,P=0.474]。结论PEG-rhG-CSF联合大剂量化疗是MM患者PBSCM的有效方案,其动员费用与rhG-CSF相当。PEG-rhG-CSF可能是MM患者PBSCM的更好选择。 相似文献
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注射用重组人淋巴毒素α衍生物Ⅰ期临床耐受性研究 总被引:1,自引:1,他引:0
背景与目的:注射用重组人淋巴毒素α衍生物(rhLTα-Da)是我国研制的一全新抗肿瘤生物制品。本研究旨在考察肿瘤患者对rhLTα-Da的耐受性,确定人体的最大耐受剂量(MTD),推荐Ⅱ期临床试验剂量。方法:剂量递增Ⅰ期临床试验。rhLTα-Da剂量分3级,即10μg·(m·2d)-1、20μg·(m·2d)-1和33μg·(m·2d)-1,每剂量组至少有3例患者。将rhLTα-Da溶于5%葡萄糖注射液100ml,静脉恒速滴注30min,每天1次,连续5天。结果:24例患者入组。主要不良反应为发热和寒战,为Ⅰ~Ⅲ度,发生率79.2%(19/24),消炎痛可一定程度减轻寒战和发热,其它不良反应包括呼吸困难(3/24)、恶心呕吐(3/24)、头痛(4/24)、乏力(2/24)、血压下降(2/24)和放疗区皮肤感觉异常(2/24)等,血生化指标未见明显的肝肾功能异常。剂量限制性毒性见于33μg·(m·2d)-1剂量组,表现为1例Ⅲ度寒战,1例Ⅲ度发热,1例Ⅲ度呼吸困难。在本临床研究的剂量范围内,未见rhLTα-Da的明确疗效,但在个别肿瘤患者(恶性黑色素瘤、皮肤蕈样霉菌病和肾癌)中看到部分病变好转。结论:rhLTα-Da的MTD为33μg·(m·2d)-1,推荐Ⅱ期临床试验剂量为20μg·(m2·d)-1。 相似文献
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The effects of human recombinant granulocyte/macrophage colony-stimulating factor (GM-CSF) and human native purified granulocyte colony-stimulating factor (G-CSF) on the growth of clonogenic leukemic blast cells from eight Japanese patients with acute myeloblastic leukemia were studied, using an in vitro leukemic blast colony assay. The results showed that GM-CSF stimulated leukemic blast colony formation in all cases examined, whereas G-CSF stimulated colony formation in four of the eight cases. The maximum stimulating activity of GM-CSF on the growth of clonogenic leukemic blast cells was higher than that of G-CSF in the majority of cases, while sometimes GM-CSF and G-CSF worked synergistically. Thus, the clonogenic leukemic blast cell populations seemed to be heterogeneous with respect to their in vitro response to growth regulators. 相似文献
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M H Bronchud J H Scarffe N Thatcher D Crowther L M Souza N K Alton N G Testa T M Dexter 《British journal of cancer》1987,56(6):809-813
Twelve patients with advanced small cell carcinoma of the bronchus were treated by continuous infusion of recombinant human granulocyte colony-stimulating factor (rhG-CSF) at the following dose levels: 1 microgram, 5 micrograms, 10 micrograms, 20 micrograms and 40 micrograms kg-1 day-1 for 5 days. No toxicities resulted from the treatment and in all 12 patients the number of peripheral neutrophils increased rapidly to a maximum of 100 x 10(9) l-1 at 10 micrograms kg-1 day-1. The neutrophils were shown to be functionally normal in tests of their mobility and bactericidal activity. During the phase II part of the study the patients were treated by a combination of intravenous adriamycin 50 mg m-2, ifosfamide 5 g m-2 by i.v. infusion with mesna 8 g m-2 on day 1, and etoposide 120 mg m-2 on days 1, 2 and 3 also intravenously. The chemotherapy regime was repeated every 3 weeks. RhG-CSF was given to each patient for 14 days on alternate cycles of chemotherapy and reduced the period of absolute neutropenia considerably (median of 80%), with a return to normal, or above normal, neutrophil counts within 2 weeks after day 1 of chemotherapy. Six severe infective episodes were observed during the cycles of chemotherapy which did not include rhG-CSF, while no infective episodes occurred when patients were treated with rhG-CSF. These results demonstrate the utility of rhG-CSF in restoring functional neutrophils to patients undergoing intensive chemotherapy. 相似文献
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Patrick J. Creaven John E. Plager Sherry Dupere Robert P. Huben Hiroshi Takita Arnold Mittelman April Proefrock 《Cancer chemotherapy and pharmacology》1987,20(2):137-144
Summary A phase I and pharmacokinetic study of recombinant tumor necrosis factor (rH-TNF Asahi) was carried out in 29 patients, who received a total of 72 courses with doses ranging from 1 to 48x104 units/m2. Drug was given as 1-h i. v. infusions. Acute toxicities, taking the form of fever, chills, tachycardia, hypertension, peripheral cyanosis, nausea and vomiting, headache, chest tightness, low back pain, diarrhea and shortness of breath, were seen, but were not dose-limiting or dose-related. Some early rise in SGOT, without any change in serum bilirubin, was noted at the highest doses. Eosinophilia, monocytosis, mild hypocalcemia and an increase in fibrin degradation products were seen in a few patients. The dose-limiting toxicity was hypotension, which occurred after the end of the drug infusion and was seen in all 5 patients treated at the highest dose. There was no mortality or long-term morbidity. There were no responses. Pharmacokinetic studies indicated a rapid plasma clearnance and a short plasma half-life, generally less than 0.5 h. 相似文献
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【摘要】 目的 观察重组人粒细胞集落刺激因子(rhG-CSF)预防化疗后中性粒细胞减少症的有效性和安全性。方法 采用随机对照方法,初治恶性肿瘤患者接受1个周期的化疗,其中治疗组化疗前24 h给予rhG-CSF 150 μg皮下注射1次,对照组不给予rhG-CSF。结果 入组52例肿瘤患者,分为治疗组和对照组各26例,WBC<4.0×109/L的发生率分别为19.23 %和53.85 %(P<0.05),白细胞减少发生率Ⅰ度分别为7.69 %和19.23 %,Ⅱ度7.69 %和15.39 %,Ⅲ度3.85 %和1.54 %,Ⅳ度0和7.69 %; 持续时间分别为1.27 d和4.04 d(P<0.05);抗生素使用率分别为7.69 %和26.92 %(P<0.05);发热性中性粒细胞减少发生率分别为3.85 %和26.92 %(P<0.05)。rhG-CSF的毒副作用主要为骨骼肌肉疼痛、乏力、头晕等。结论 化疗前应用rhG-CSF能有效控制肿瘤化疗后白细胞减少的发生,降低肿瘤化疗后白细胞减少的程度。 相似文献
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P J O'Dwyer F P LaCreta R Schilder S Nash C McAleer L L Miller G R Hudes R F Ozols 《Journal of clinical oncology》1992,10(8):1352-1358
PURPOSE: The ability of growth factors to stimulate marrow recovery suggests their potential for use in dose intensification of cytotoxic drugs. We performed a phase I study of the alkylating agent thiotepa in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), with the goal of dose-escalation of thiotepa. Thiotepa was selected based on its capacity for dose escalation to more than 1 g/m2 in the marrow transplantation setting. PATIENTS AND METHODS: The starting dose of thiotepa (75 mg/m2) was the highest dose evaluated in our previous phase I trial. Thirteen patients received 22 courses of thiotepa and GM-CSF. The dose of GM-CSF was 10 micrograms/kg subcutaneously daily in six patients and 5 micrograms/kg in seven patients. RESULTS: Three patients (23%) developed grade 3 to 4 neutropenia on the first course, with a recovery to more than 1000/mm3 in 4.7 days (mean). Recovery was as rapid with the 5 micrograms/kg as it was with the 10 micrograms/kg GM-CSF dose. Thrombocytopenia grade 3 to 4 affected seven of 13 (54%) patients in the first course; counts recovered to more than 50,000/mm3 in a median of 15 days. GM-CSF at either dose did not influence markedly the severity or duration of thrombocytopenia, and did not permit dose escalation of thiotepa. Among the seven patients who received a second cycle of treatment, six of seven experienced grade 3 or 4 thrombocytopenia that lasted a median of 15.5 days. Five had thrombocytopenia that lasted more than 35 days after one to three cycles of treatment. Plasma concentrations of thiotepa and tepa were measured by gas chromatography in eight patients. The plasma elimination of thiotepa fit a two-compartment open model with a harmonic mean terminal half-life of 2.44 hours. The mean total body clearance was 217.9 mL/min/m2, and the mean steady-state volume of distribution (Vdss) was 36.8 L/m2. The half-life of tepa was 7.98 hours, and the ratio of the area under the plasma concentration versus time curve (AUC) of tepa to that of thiotepa was 0.79. CONCLUSIONS: These data were consistent with our previous observations at this dose, and indicated that the severity of toxicity in these patients was not explained by aberrant pharmacokinetic indices. We conclude that, independent of effects on neutropenia, severe and cumulative platelet toxicity precludes further escalation of thiotepa dose despite the use of GM-CSF. 相似文献
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20.
目的 观察重组人粒细胞集落刺激因子(rhG-CSF)对鼻咽癌急性放射性口腔黏膜损伤的作用。方法 将50例鼻咽癌住院患者随机分为对照组和rhG CSF治疗组,每组25例。对照组用生理盐水每次10ml含漱,治疗组用生理盐水100ml+rhG-CSF900μg溶液每次10ml含漱;每日3~5次,每次10分钟。两组均采用标准分割方式放疗,观察急性口腔黏膜损伤的发生率、严重程度及其疗效。结果 放疗20Gy时治疗组的黏膜损伤发生率为40%,对照组为68%(P=0.047)。放疗结束治疗组的1~4级黏膜损伤发生率分别为44%、24%、12%和0,对照组分别为16%、28%、44%和8%(P<0.05)。治疗组患者的生活质量各项指标均较对照组有明显改善(P<0.05)。结论 rhG-CSF能够降低鼻咽癌急性放射性黏膜损伤的发生率,并减轻其损伤程度,值得推广。 相似文献