Biason P, Masier S, Toffoli G
Clinical and Experimental Pharmacology Division, CRO-Centro di Riferimento Oncologico, National Cancer Unstitute, Aviano, Italy.
J Chemother. 2008 Apr;20(2):158-65. doi: 10.1179/joc.2008.20.2.158.
Irinotecan is a drug commonly used for the treatment of cancer patients, both as a single agent or in combination therapy. Neutropenia and diarrhea are the dose-limiting toxicities. Genetic variations of proteins involved in irinotecan metabolism and transport have been considered in the development of irinotecan toxicity. In particular, polymorphisms affecting UDP-glucuronosyltransferase isoform 1A1 (UGT1A1) expression or activity are being investigated. Among these, UGT1A128 has been considered as the major predictive pharmacogenetic marker for severe hematological toxicity (neutropenia). However, translation to clinical practice of UGT1A128 testing as a predictive marker of adverse effects needs to be further investigated and the available data are not conclusive in defining a precise genotype-based dosage. Further prospective studies are required to reach a personalization of chemotherapy with irinotecan.
伊立替康是一种常用于治疗癌症患者的药物，可单独使用或用于联合治疗。中性粒细胞减少和腹泻是剂量限制性毒性反应。伊立替康代谢和转运相关蛋白的基因变异在伊立替康毒性的研究中受到关注。特别是，影响尿苷二磷酸葡萄糖醛酸基转移酶同工酶1A1（UGT1A1）表达或活性的多态性正在研究中。其中，UGT1A128被认为是严重血液学毒性（中性粒细胞减少）的主要预测性药物遗传学标志物。然而，将UGT1A128检测作为不良反应预测标志物应用于临床实践仍需进一步研究，现有数据在确定基于精确基因型的剂量方面尚无定论。需要进一步的前瞻性研究来实现伊立替康化疗的个体化。
