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
neoplasm
tumor necrosis factor
clinical trial,phase Ⅰ
dosage
side effect
tolerance
