Correlation between nUGT1A1 gene polymorphisms and adverse events of irinotecan plus S-1 for patients with recurrent or metastatic esophageal squamous cell carcinoma: a prospective, open-label, randomized controlled trial (ESWN 01)
10.3760/cma.j.cn112152-20191022-00678
- VernacularTitle:尿苷二磷酸葡萄糖醛酸转移酶1A1基因多态性与伊立替康联合替吉奥治疗晚期食管鳞癌所致不良反应的关系
- Author:
Xi WANG
1
;
Ying LIU
;
Junxing HUANG
;
Ping LU
;
Yi BA
;
Lin WU
;
Yuxian BAI
;
Shu ZHANG
;
Jifeng FENG
;
Ying CHENG
;
Jie LI
;
Lu WEN
;
Xianglin YUAN
;
Changwu MA
;
Chunhong HU
;
Qingxia FAN
;
Binghe XU
;
Jing HUANG
Author Information
1. 国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院内科 100021
- Keywords:
Esophageal squamous cell carcinoma;
Irinotecan;
Adverse events;
Uridine diphosphate glucoronosyltransferase 1A1;
Gene polymorphisms;
Diarrhea;
Neutropenia
- From:
Chinese Journal of Oncology
2021;43(11):1177-1182
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the correlation between UGT1A1 polymorphisms and the irinotecan plus S-1 regimen-induced toxicities in Chinese advanced esophageal squamous cell carcinoma (ESCC) patients.Methods:A total of 46 recurrent or metastatic ESCC patients selected from ESWN 01 trial were randomly assigned to irinotecan plus S-1 group [intravenous infusion of irinotecan (160 mg/m 2) on day 1 and oral S-1 (80-120 mg) on days 1-10, repeated every 14 days]. Peripheral venous blood at baseline was collected and genomic DNA was extracted. The genetic polymorphisms of UGT1A1*6 and UGT1A1*28 were analyzed by polymerase chain reaction (PCR) amplification. Irinotecan plus S-1 regimen-induced toxicities of patients with different UGT1A1 polymorphisms were observed. The correlation between UGT1A1 polymorphisms and the adverse effects was analyzed. Results:Among the 46 patients, the numbers of UGT1A1*6 wild type genotype (GG), mutant heterozygote (GA) and mutant homozygote (AA) were 30, 15 and 1, while those with UGT1A1*28 wild type genotype (TA6/6), mutant heterozygote (TA6/7) and mutant homozygote (TA7/7) were 36, 8 and 2, respectively. Only one patient with UGT1A1*6 AA genotype occurred grade 3 diarrhea, while one of the 2 patients with UGT1A1*28 TA7/7 genotype occurred grade 4 diarrhea. No neutropenia was observed in the patient with UGT1A1*6 AA genotype, however, both of the two patients with UGT1A1*28 TA7/7 genotype occurred grade 3-4 neutropenia. Patients with UGT1A1*28 genetic polymorphism (TA 6/7 or TA7/7) had a higher response rate compared with wild-type TA6/6 carriers. (55.6% versus 26.5%).Conclusions:The homozygous genotype of UGT1A1*6 AA and UGT1A1*28 TA7/7 are rare (<5%) in Chinese ESCC population. Not all homozygous AA and TA7/7 carriers occur severe dose limited toxicities (DLT) when treated with irinotecan (160 mg/m 2) plus S-1 regimen for 2 weeks. However, it′s still necessary torigorously observe the occurrence of severe diarrhea and neutropenia in patients with UGT1A1*6 AA and UGT1A1*28 TA7/7 and adjust the dose timely.
