重组人肿瘤坏死因子衍生物K2Ⅰ期临床耐受性研究  

Phase Ⅰ Clinical Trial(Tolerance Test)of Derivant of Recombinant Human Tumor Necrosis Factor

作　　者：陈强[1] 刘健[1] 张其忠[1] 毛雪华[1] 杨建伟[1] 黄萍[1] 范南峰[1] 

机构地区：[1]福建省肿瘤医院,福建福州350014

出　　处：《浙江肿瘤》2000年第3期135-137,共3页

摘　　要：目的]确定重组人肿瘤坏死因子衍生物(rhTNFα DK2)的人体可耐受剂量范围或最大耐受剂量 ,观察其毒性表现。[方法]设计6个剂量组 ,每组3例 ,以30万IU/m2 为初始剂量 ,按60、90、120、150和200万IU/m2 剂量渐次递增 ,受试病人在2小时内静脉滴注250ml药液 ,每日1次 ,连续7天。[结果]20例肿瘤病人入组 ,除2例因故出组外 ,其余18例均按计划完成试验。临床观察到的主要毒副反应为畏冷、寒战、发热、血压异常、白细胞下降及骨肌肉酸痛等 ,多属Ⅰ级可逆反应(WHO分级) ,未发现有Ⅲ级以上毒性反应 ,毒性反应发生的程度和发生率与剂量无明显相关 ,全部病人的肝肾功能和尿常规在用药前后均在正常值范围内。[结论]200万IU/m2(含200万IU/m2)以下的剂量对人体都是可耐受的安全剂量。To determine the effective biological dose and/or maximum tolerated dose of the derivant of recombinant human tumor necrosis factor(rhTNFαDK2) Patients were randomized to the one of six treatment groups with the escalating doses:300 000 IU/m2;600 000IU/m2;900 000IU/m2;1 200 000IU/m2;1 500 000IU/m2;2 000 000IU/m2Each group included 3 patientsThe patients received the drug in 250ml ivin 2 hours,once a day,for 7 consecutive daysOf 20 patients, 2 discontinued the trial because of patients refusing and 18 finished the trialThe main side effect were chilly,shiver,fever,abnormal blood pressure,leukopenia,and aching pain in muscles,etcThe most side effects were grade Ⅰ. It was reversable The side effects over Ⅲ degree not foundThere was no obvious relationship between the dose and the grade of side effectAll patients liver function,kidney function,urine routine test were in normal range before and after drug administration[Conclusion]It shows a dose of ≤2 000 000IU/m2 is safe and tolerant for human

关 键 词：肿瘤坏死因子 临床试验 耐受性 RHTNF 肿瘤 

分 类 号：R979.1[医药卫生—药品] R730.53[医药卫生—药学]