Yan Yulan, Mo Yongsen, Zhang Dongmei
Department of Hematologly, the Fifth Central Hospital in Tianjin, Tianjin 300450, China.
Zhonghua Gan Zang Bing Za Zhi. 2015 Mar;23(3):204-8. doi: 10.3760/cma.j.issn.1007-3418.2015.03.010.
To investigate the preventive effect of magnesium isoglycyrrhizinate against acute drug-induced liver damage from initial chemotherapy treatment in patients with gastrointestinal cancer.
A total of 216 cases with early stage gastric cancer and indications for systemic chemotherapy that had been diagnosed with gastrointestinal malignant tumors by pathology in our hospital were enrolled for study during the period of January 2011 to June 2013.Using a prospective randomized controlled study design,differences were assessed between groups treated with glycyrrhizic acid magnesium (experimental group; n=114) or glutathione (control group; n=102) and the FOLFOX regimen (n=104) or the XELOX regimen (n=112).Patients in the FOLFOX group received intravenous infusion of L-OHP (85 mg/m²) at day 1,followed by a bolus injection of 5-FU (400 mg/m²) at days 1-2 and continuous intravenous infusion of 5-FU (600 mg/m²) for 22 h at days 1-2,with one cycle comprising 2 weeks. Patients in the XELOX group received intravenous infusion of L-OHP (130 mg/m²) at day 1, followed by capecitabine (1 000 mg/m²) oral twice a day at days 1-14,with one cycle comprising 3 weeks.In the first cycle of chemotherapy,serum was extracted from the patients at 1 day before chemotherapy and 1 week after chemotherapy.An automated biochemistry analyzer was used to measure alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil) and alkaline phosphatase (ALP). Differences between groups were statistically analyzed by the t-test and x² test.
Among the total 216 cases treated with chemotherapy,40 showed hepatic biochemical abnormalities (12 cases in the experimental group, 28 cases in the control group), and the effect of prevention was significantly different between the two groups (10.53% vs. 27.25%; x² =10.219, P less than 0.005).The acute and subacute hepatic toxicity reaction degrees for the experimental and the control groups were: 0:94.78% vs. 88.2%; 1:5.3% vs. 11.8% (x² =6.99, P < 0.01). One week after chemotherapy, the liver biochemical indexes in the experimental group (ALT:35.93 ± 8.33 U/L; AST:24.84 ±2.91 U/L; TBil:13.29 ± 5.89 mumol/L; ALP:125.1 ± 53.61 U/L) were statically different from those in the control group (all P < 0.05). The liver biochemical indexes before and after chemotherapy were also significantly different between the experimental group (ALT:13.18t3.23 U/L; AST:5.39 ± 2.57 U/L; TBil:2.79 ± 0.23 mumol/L; ALP:52.08 ± 4.83 U/L) and the control group (all P < 0.05).One week after chemotherapy in the experimental group, the groups treated with the FOLFOX regimen or the XELOX regimen showed no statistical differences in the liver biochemical indexes.One week after chemotherapy in the control group, though, the groups treated with the FOLFOX regimen showed significantly lower AST (26.24 ± 3.50 U/L vs. 29.80 ± 6.57 U/L, t=-2.431, P < 0.05),but the residual liver biochemical indexes were not significantly different.In the experimental group, the FOLFOX group showed significantly lower ALP (53.44 ± 2.47 U/L vs. 56.58 ± 6.70 U/L, t =-2.201, P < 0.05), AST (6.48 ± 3.15U/L vs. 9.88 ± 4.57 U/L, t =-5.223, P < 0.05), but the residual liver biochemical index was not significantly different.
Magnesium isoglycyrrhizinate is an effective drug for the prevention of drug-induced liver damage after initial chemotherapy in patients with early stage gastrointestinal cancer.
探讨异甘草酸镁对胃肠道癌患者初始化疗所致急性药物性肝损伤的预防作用。
选取2011年1月至2013年6月在我院经病理确诊为胃肠道恶性肿瘤且有全身化疗指征的早期胃癌患者216例进行研究。采用前瞻性随机对照研究设计,评估异甘草酸镁治疗组(实验组;n = 114)或谷胱甘肽治疗组(对照组;n = 102)与FOLFOX方案治疗组(n = 104)或XELOX方案治疗组(n = 112)之间的差异。FOLFOX组患者于第1天静脉输注L-OHP(85 mg/m²),随后在第1 - 2天静脉推注5-FU(400 mg/m²),并在第1 - 2天持续静脉输注5-FU(600 mg/m²)22小时,每2周为1个周期。XELOX组患者于第1天静脉输注L-OHP(130 mg/m²),随后在第1 - 14天口服卡培他滨(1 000 mg/m²),每日2次,每3周为1个周期。在化疗的第1周期,于化疗前1天和化疗后1周采集患者血清。采用自动生化分析仪检测丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBil)和碱性磷酸酶(ALP)。组间差异采用t检验和x²检验进行统计学分析。
在接受化疗的216例患者中,40例出现肝脏生化异常(实验组12例,对照组28例),两组预防效果差异有统计学意义(10.53%对27.25%;x² = 10.219,P < 0.005)。实验组和对照组的急性和亚急性肝毒性反应程度为:0级:94.78%对88.2%;1级:5.3%对11.8%(x² = 6.99,P < 0.01)。化疗后1周,实验组肝脏生化指标(ALT:35.93 ± 8.33 U/L;AST:24.84 ± 2.91 U/L;TBil:13.29 ± 5.89 μmol/L;ALP:125.1 ± 53.61 U/L)与对照组相比差异有统计学意义(均P < 0.05)。实验组化疗前后肝脏生化指标(ALT:13.18 ± 3.23 U/L;AST:5.39 ± 2.57 U/L;TBil:2.79 ± 0.23 μmol/L;ALP:52.08 ± 4.83 U/L)与对照组相比差异也有统计学意义(均P < 0.05)。化疗后1周,实验组中接受FOLFOX方案或XELOX方案治疗的患者肝脏生化指标差异无统计学意义。然而,化疗后1周,对照组中接受FOLFOX方案治疗的患者AST显著降低(26.24 ± 3.50 U/L对29.80 ± 6.57 U/L,t = -2.431,P < 0.05),但其余肝脏生化指标差异无统计学意义。在实验组中,FOLFOX组的ALP(53.44 ± 2.47 U/L对56.58 ± 6.70 U/L,t = -2.201,P < 0.05)、AST(6.48 ± 3.15 U/L对9.88 ± 4.57 U/L,t = -5.223,P < 0.05)显著降低,但其余肝脏生化指标差异无统计学意义。
异甘草酸镁是预防早期胃肠道癌患者初始化疗后药物性肝损伤的有效药物。