UGT1A1*28基因多态性与中药预防伊立替康腹泻效果的关系

  目的  探讨中药对伊立替康化疗后腹泻的预防作用，同时结合尿苷二磷酸葡萄糖醛酸转移酶1A1*28（UGT1A1*28）基因多态性进行中药疗效分析。  方法  自2011年10月至2013年5月共200例患者被随机分为对照组（单纯化疗）和中药组（化疗联合中药）。全部患者在化疗开始前均接受UGT1A1*28基因多态性的检测。化疗采用标准FOLFIRI方案，中药于化疗前2 d开始服用，至伊立替康化疗后第5天结束。期间记录患者不良反应，并进行疗效评价。  结果  200例患者中TA6/6野生基因型144例，非野生基因型56例（TA7/7纯合型12例和TA6/7杂合型44例）。2级以上腹泻者共58例，中药组腹泻发生率较对照组下降14%（22% vs. 36%，P=0.029）。除腹泻以外，2级以上呕吐发生率中药组也明显低于对照组（15% vs. 27%，P=0.037）。患者总体有效率为37.5%，中药组和对照组相比差异无统计学意义（40% vs. 35%，P=0.465）。UGT1A1*28野生基因型患者2级以上腹泻发生率（22.9% vs. 44.6%，P=0.002）和呕吐发生率（16.7% vs. 23.2%，P=0.016）均低于与非野生基因型患者。在中药治疗组中，非野生基因型与野生型相比，2级以上腹泻发生率（22.2% vs. 21.9%，P=0.974）和呕吐发生率（18.5% vs. 13.7%，P=0.777）差异无统计学意义。  结论  中药可有效预防伊立替康引起的迟发性腹泻，对于UGT1A1*28非野生基因型患者的迟发性腹泻同样具有预防作用。UGT1A1*28基因非野生基因型腹泻发生率明显高于野生基因型，在使用伊立替康治疗前应检测患者的该基因状态。 

Effect of herbs on preventing diarrhea caused by irinotecan and its correlation with gene polymorphism of UGT1A1*28

  Objective  This study aimed to determine the function of herbs in preventing diarrhea after irinotecan chemotherapy and analyze the efficacy of the herbs based on UGT1A1*28 gene polymorphism.  Methods  A total of 200 patients admitted to the Department of Synergistic Chinese and Western Medicine, Tianjin Medical University Cancer Institute and Hospital between October 2011 and May 2013 were randomly divided into the control (chemotherapy alone) and herb (chemotherapy combined with herbs) groups. All patients consented to UGT1A1*28 gene polymorphism detection prior to chemotherapy. Herbs were administered from 2 d prior to chemotherapy to 5 d post chemotherapy, with or without the regimen of fluorouracil, folinic acid, and irinotecan. Adverse reactions were recorded, and short-term effect was evaluated regularly.  Results  A total of 144 patients had TA6/6 wild genotype, and another 56 patients had non-wild genotype (12 of the 56 cases were TA7/7 homozygous, and the other 44 cases were TA6/7 hybrid). A total of 58 patients experienced grades 2 to 4 diarrhea. A 14% decrease in the incidence of diarrhea was observed in the herb group compared with that of the control group (22% vs. 36%, P=0.029). In addition to diarrhea, grades 2 to 4 vomiting was significantly lower in the herb group than in the control group (15% vs. 27%, P=0.037). The overall response rate was 37.5%. No significant difference was found between the two groups (40% vs. 35%, P=0.465). The incidences of grades 2 to 4 diarrhea (22.9% vs. 44.6%, P=0.002) and grades 2 to 4 vomiting (23.2% vs. 16.7%, P=0.016) were lower in patients with the UGT1A1*28 wild genotype than in those with the non-wild genotype. However, in the herb group, the incidences of grades 2 to 4 diarrhea (22.2% vs. 21.9%, P=0.974) and vomiting (18.5% vs. 13.7%, P=0.777) were not significant between the non-wild- and wild-type groups.  Conclusion  Herbs can effectively prevent the late diarrhea caused by irinotecan, which is also applicable in UGT1A1*28 non-wild genotype patients. Incidence of diarrhea was obviously higher in the cases with UGT1A1*28 non-wild type than in those with wild genotype. Hence, the UGT1A1*28 gene type should be detected prior to chemotherapy with irinotecan.