UGT1A1*20 and other UGT1A polymorphisms as determinants of irinotecan toxicity

被引：26

作者：

Biason, P. ^{[1
]}

Masier, S. ^{[1
]}

Toffoli, G. ^{[1
]}

机构：

[1] Natl Canc Inst, Ctr Riferimento Oncol, Clin & Expt Pharmacol Div, I-33081 Aviano, PN, Italy

来源：

JOURNAL OF CHEMOTHERAPY | 2008年 / 20卷 / 02期

关键词：

CRC : colorectal cancer; SN38 : 7-ethyl-10-hydroxycamptothecin; hCE : human carboxylesterases; APC : 7-ethyl-10-[4-N-(5-amino pentanoic acid)-1-piperidino]-carbonyloxycamptothecin; NPC : 7-ethyl-10-[4-(1-piperidino)-1-amino]-carbonyloxycamptothecin; UGT : UDP-glucuronosyltransferase; SNP : Single Nucleotide Polymorphism; LD : Linkage Disequilibrium;

D O I：

10.1179/joc.2008.20.2.158

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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, UGT1A1*28 has been considered as the major predictive pharmacogenetic marker for severe hematological toxicity (neutropenia). However, translation to clinical practice of UGT1A1*28 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.

引用

页码：158 / 165

页数：8

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