异甘草酸镁注射液预防抗肿瘤化疗相关性急性肝损伤的随机对照、全国多中心临床研究MAGIC-临床研究协作组【期刊名称】《临床肿瘤学杂志》【年(卷),期】2017(022)002【摘要】Objective Anti-tumor cytotoxic drug is one kind of the most common drugs causing drug-induced liver injury ( DILI) . This study aimed to observe and evaluate the efficacy and safety of magnesium isoglycyrrhizinate injection ( MgIG) for preven-tion of chemotherapy-induced acute liver injury in a large-scale population with malignant tumors. Methods It was a prospective, open-label, randomized controlled and nationwide multi-center study( MAGIC-301 Study) . Patients who received the chemotherapy reg-imen containing one of the following four chemotherapy drugs or more, cisplatin(≥60 mg/m2 ) , oxaliplatin(≥85mg/m2 ) , cyclophos-phamide(≥600 mg/m2) and gemcitabine(≥2000mg/m2), were randomized to the MgIG group and the control group. The MgIG group was assigned to receive MgIG injection 200mg/d ivgtt one day before the start of chemotherapy and lasting for at least 5 days.The control group was assigned to receive only chemotherapy regimen without MgIG injection. Referring to National Cancer Institute-Common Terminology Criteria for Adverse Events( NCI-CTC AE) version 4. 0, the occurrence of liver injury, including the incidence and severity degree, wasstrictly observed and compared both before and after chemotherapy. Rescue hepatoprotective treatments were administered if necessary. Results The study was carried out at 28 cancer centers in China between February 28, 2013 and December 31, 2015. A total of 1200 patients were enrolled into the study. Of these patients, 1146 ( 95. 5%) patients were included in the full a-nalysis set ( FAS ) and randomized to the MgIG group ( n= 766 ) and the control group ( n= 380 ) respectively. The baseline demographics and clinical characteristics, including age, gender, weight, history of liver disease, type of malignancy and chemotherapy regimen etc, were well balanced between the groups(P>0. 05). In the FAS, 62. 63% of patients in the control group presented with liver injury after the chemotherapy, while 52. 81% in the MgIG group( P=0. 0004) . The analyses of NCI grading for the severity of liver injury showed that the incidence of grade 2 or more liver function abnormity was 12. 37% in the control group and 10. 07% in the MgIG group after the chemotherapy( P=0. 0008) . In addition, 32. 37% of patients presented with the elevation of liver injury grade for at least one level in the control group,which increased by 11. 17% compared with the MgIG group ( P<0. 0001) . In the MgIG group, the incidence of the liver function abnormity decreased by 7. 11% ( P=0. 0188) , 22. 36% ( P=0. 0033) and 18. 71%( P=0. 0380) respectively in the different chemotherapy regimens containing platinum drugs, cyclophosphamide or gemcitabine. The incidence of alanine aminotransferase (ALT) and glutamicoxaloacetic transaminase(AST) abnormity in the MgIG group were signifi-cantly lower than those in the control group after chemotherapy.On the second week of chemotherapy ( d13-d15) , the incidence of ALT and AST abnormity decreased significantly in the MgIG group, which reduced by 50% compared with the control group ( ALT:8. 63%vs. 16. 58%, P<0. 0001;AST:10. 72% vs. 20. 05%, P<0. 0001) . During the study period, the rescue treatments were administered in 1. 3% of patients in the MgIG group, while occurring in 9. 2% of patients in the control group ( P<0. 0001) . The incidence of AE was similar between the two groups. Conclusion The study results suggest that the DILI induced by the chemotherapy containing the platinum drug, cyclophosphamide or gemcitabine was characterized by the higher incidence and the more serious hazardness. Thus, more attention should be paid, especially to enhance the surveillance of liver function in the whole course and the management of liver injury in the clinical practice. Prophylaxis with MgIG injection can significantly reduce the incidence and severity of DILI before the chemotherapy initiation and during the concurrent chemotherapy. It is worthy of investigation further and clinical application widely.%目的抗肿瘤细胞毒性药物是引起药物性肝损伤(DILI)最常见的药物之一.本研究旨在观察和评价在大样本恶性肿瘤患者人群中采用异甘草酸镁注射液预防抗肿瘤化疗相关性急性肝损伤的有效性和安全性.方法采取前瞻性、开放性、随机对照、全国多中心的临床协作研究(简称MAGIC-301研究).对使用含顺铂(≥60 mg/m2)、奥沙利铂(≥85 mg/m2)、环磷酰胺(≥600 mg/m2)或吉西他滨(≥2000 mg/m2)四种细胞毒药物中任意一种或数种进行化疗的恶性肿瘤患者,随机分为两组.试验组于随机化疗的前1天起,给予异甘草酸镁注射液200 mg/d,静脉滴注,连续使用≥5天;对照组仅给予常规化疗.至1个化疗疗程结束,参照NCI-CTC AE 4.0版标准,严格观察和比较患者化疗前、后肝损伤的发生情况,包括发生率和严重程度,必要时给予解救性保肝方案治疗.结果全国28家研究中心共同参与,2013年2月28日至2015年12月31日共入组病例1200例,其中1146例(95.50%)纳入全分析集(FAS)分析,试验组和对照组分别为766例和380例.两组患者入组前的人口学信息,包括年龄、性别、体重、既往肝病史、癌种以及化疗方案等情况均衡可比(P>0.05).FAS分析显示,化疗后对照组的肝损伤发生率达62.63%,试验组为52.81%(P=0.0004);根据肝损伤严重程度NCI分级分析显示,化疗后,对照组2级以上肝功能异常率为12.37%,而试验组为10.07%(P=0.0008),且对照组有32.37%的患者上升了至少1个肝损伤等级,相较于试验组高出11.17%(P<0.0001).分别统计含铂类、含环磷酰胺和含吉西他滨的不同化疗方案,试验组的肝损伤发生率较对照组分别降低7.11%(P=0.0188)、22.36%(P=0.0033)和18.71%(P=0.0380).化疗后肝功能指标ALT和AST的异常率,试验组也显著低于对照组;化疗第2周(13~15天)试验组的ALT及AST异常率较对照组均降低近50%(ALT异常率:8.63%vs.16.58%,P<0.0001;AST异常率:10.72%vs.20.05%,P<0.0001).在整个试验过程中,试验组发生解救用药情况的解救率为1.3%,而对照组高达9.2%(P<0.0001).两组其他不良事件和不良反应的发生率基本相当.结论上述大样本研究结果和数据分析表明,含铂类、含环磷酰胺和含吉西他滨化疗引起的DILI发生率较高、危害程度较重,在临床实践过程中应该高度重视,加强对肝功能的全程监控与肝损伤的防治.在化疗前和化疗同时,预防性应用异甘草酸镁注射液可以明显降低以上药物化疗相关性急性肝损伤的发生率及其严重程度,值得进一步深入研究和临床推广应用.【总页数】10页(P97-106)【作者】MAGIC-临床研究协作组【作者单位】【正文语种】中文【中图分类】R730.6【相关文献】1.异甘草酸镁注射液治疗抗结核药物所致急性肝损伤的临床研究 [J], 郭新枝;陈裕;程俊伟;陈永芳;张晓慧;王志刚;刘宝琴2.异甘草酸镁治疗抗肿瘤药物所致急性药物性肝损伤的治疗效果、不良反应及肝功能恢复情况 [J], 孔珊珊3.异甘草酸镁注射液预防化疗后肝损伤的临床研究 [J], 陈丹红;徐伟4.双环醇预防恶性血液病患者化疗后急性药物性肝损伤的前瞻性随机对照研究 [J], 杨栋林;何祎;翟卫华;弓晓媛;石茵;刘庆珍;吕瑞;白雪莲;周卢琨5.异甘草酸镁注射液预防血液肿瘤化疗相关肝损伤多中心临床协作研究 [J], 李国辉;田培军;张福林;贺鹏程;葛繁梅;王一;宋艳萍;耿惠;王存邦;王景昌;刘利;陈任安;王文清;秦炜炜;赵万红;姚亚洲;张启科;张亚莉;黄国强因版权原因，仅展示原文概要，查看原文内容请购买。
