伊立替康
腹泻
医学
内科学
药理学
序号38
生物标志物
中性粒细胞减少症
临床试验
化疗
肿瘤科
癌症
结直肠癌
生物
生物化学
作者
Ali N. Chamseddine,Michel Ducreux,Jean‐Pierre Armand,Xavier Paolettí,Tuvana Satar,Angélo Paci,Olivier Mir
标识
DOI:10.1016/j.pharmthera.2019.03.002
摘要
Irinotecan is an anticancer drug with a broad spectrum of activity, characterized by multistep and complex pharmacology. Regardless of its schedule of administration, neutropenia and delayed-type diarrhea are the most common side effects. The latter was the dose-limiting toxicity in phase I trials, and its prediction by pharmacogenetic (UGT1A1*28/*28) testing remains sub-optimal. Recent studies have highlighted the important role of the intestinal bacterial β-glucuronidase (BGUS) in the onset of irinotecan-induced diarrhea. Intestinal BGUS hydrolyses glucuronidated metabolites to their toxic form in intestines, resulting in intestinal damage. BGUS selective inhibitors that are currently in development may alleviate irinotecan-induced diarrhea, and may help to reduce its morbidity and enhance its activity. The discussion and description of irinotecan pharmacology may generate ideas that form the basis of clinical trials focusing on a personalized approach to treatment. In addition, we hypothesize that using BGUS activity as a predictive biomarker of irinotecan-induced diarrhea severity will help to select cancer patients for treatment with irinotecan chemotherapy (whether at full or adapted dose).
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