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首页> 外文期刊>Bulletin du Cancer: Journal de l'Association Francaise pour l'Etude du Cancer >Interest of UGT1A1 genotyping within digestive cancers treatment by irinotecan [Intérêt du génotypage de l'UGT1A1 dans le cadre du traitement des cancers digestifs par irinotécan]
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Interest of UGT1A1 genotyping within digestive cancers treatment by irinotecan [Intérêt du génotypage de l'UGT1A1 dans le cadre du traitement des cancers digestifs par irinotécan]

机译：伊立替康治疗消化系统癌症中UGT1A1基因型的兴趣[伊立替康治疗消化系统癌症中UGT1A1基因型的兴趣]

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摘要

Irinotecan is a cytotoxic agent administered by IV infusion in the treatment of advanced colorectal cancer. Its anticancer activity results from its bioactivation into SN-38 metabolite, which is cleared through glucuronidation by the hepatic enzyme uridine diphosphate- glucuronosyltransferase 1A1 (UGT1A1). In the general population, there is wide inter-subject variability in UGT1A1 enzyme activity related to UGT1A1 gene polymorphisms. The French joint workgroup coming from the National Pharmacogenetic Network (RNPGx) and the Group of Clinical Oncologic Pharmacology (GPCO) herein presents an updated review dealing with efficacy and toxicity clinical studies related to UGT1A1 genetic variants. From a critical analysis of this review it clearly emerges that, for doses higher than 180 mg/m 2, hematologic and digestive irinotecan-induced toxicities could be prevented in daily clinical practice by generalizing the use of a simple pharmacogenetic test before starting treatment. The clinical relevance of this test is also discussed in terms of treatment efficacy improvement, with the possibility of increasing the irinotecan dose in patients not bearing the deleterious allele. This test involves using a blood sample to analyze the promoter region of the UGT1A1 gene (UGT1A1*28 allele). Best execution practices, laboratory costs, as well as results interpretation are described with the aim of facilitating the implementation of this analysis in clinical routine. The existence of a French laboratories network performing this test in clinical routine makes it possible to generalize UGT1A1 deficiency screening, so as to guarantee equal access to safe treatment and optimized irinorecan-based therapy for the many patients receiving irinotecan-based therapy in advanced colorectal cancer.
机译：伊立替康是通过静脉输注施用的细胞毒性剂，用于治疗晚期大肠癌。它的抗癌活性来自其对SN-38代谢物的生物激活，该代谢物通过肝酶尿苷二磷酸-葡萄糖醛酸转移酶1A1（UGT1A1）的葡萄糖醛酸苷化作用而清除。在一般人群中，与UGT1A1基因多态性相关的UGT1A1酶活性的受试者间差异很大。来自国家药物遗传学网络（RNPGx）和临床肿瘤药理学组（GPCO）的法国联合工作组在此提供了有关与UGT1A1基因变异有关的功效和毒性临床研究的最新综述。从对该评价的严格分析中可以清楚地看出，对于高于180 mg / m 2的剂量，在日常临床实践中，可以通过在开始治疗前推广使用简单的药物遗传学测试来预防血液和消化伊立替康引起的毒性。还根据治疗功效的改善来讨论该试验的临床意义，并可能增加不携带有害等位基因的患者的伊立替康剂量。该测试涉及使用血液样本分析UGT1A1基因（UGT1A1 * 28等位基因）的启动子区域。描述了最佳执行实践，实验室成本以及结果解释，旨在促进在临床常规中实施此分析。法国实验室网络在临床常规中执行此测试的存在使对UGT1A1缺乏症筛查的一般化成为可能，从而确保许多接受伊立替康治疗的晚期大肠癌患者平等获得安全治疗和优化的基于伊力诺瑞康的治疗。

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