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

Wang Xi; Liu Ying; Huang Junxing; Lu Ping; Ba Yi; Wu Lin; Bai Yuxian; Zhang Shu; Feng Jifeng; Cheng Ying; Li Jie; Wen Lu; Yuan Xianglin; Ma Changwu; Hu Chunhong; Fan Qingxia; Xu Binghe; Huang Jing

doi:10.3760/cma.j.cn112152-20191022-00678

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

Translated title of the contribution: 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)

Wang Xi
, Liu Ying
, Huang Junxing
, Lu Ping
, Ba Yi
, Wu Lin
, Bai Yuxian
, Zhang Shu
, Feng Jifeng
, Cheng Ying
, Li Jie
, Wen Lu
, Yuan Xianglin
, Ma Changwu
, Hu Chunhong
, Fan Qingxia
, Xu Binghe
, Huang Jing

Health Science Center

Chinese Academy of Medical Sciences
Henan Cancer Hospital
Taizhou People's Hospital
Xinxiang Medical College
Tianjin Medical University
Central South University
Harbin Medical University
Shandong Cancer Hospital
Jiangsu Institute of Cancer Institute & Hospital
Jilin Cancer Hospital
Shanxi Provincial Cancer Hospital
Tongji Hospital
Chifeng Municipal Hospital
First Affiliated Hospital of Zhengzhou University

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

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/ m²) 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/ m²) 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.

Translated title of the contribution	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)
Original language	Chinese (Traditional)
Pages (from-to)	1177-1182
Number of pages	6
Journal	Zhonghua zhong liu za zhi [Chinese journal of oncology]
Volume	43
Issue number	11
DOIs	https://doi.org/10.3760/cma.j.cn112152-20191022-00678
State	Published - 23 Nov 2021

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Xi, W., Ying, L., Junxing, H., Ping, L., Yi, B., Lin, W., Yuxian, B., Shu, Z., Jifeng, F., Ying, C., Jie, L., Lu, W., Xianglin, Y., Changwu, M., Chunhong, H., Qingxia, F., Binghe, X., & Jing, H. (2021). 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. Zhonghua zhong liu za zhi [Chinese journal of oncology], 43(11), 1177-1182. https://doi.org/10.3760/cma.j.cn112152-20191022-00678

@article{260d08aa35734569b8398feaca961ea2,

title = "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",

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/ m2) 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/ m2) 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.",

keywords = "Adverse events, Diarrhea, Esophageal squamous cell carcinoma, Gene polymorphisms, Irinotecan, Neutropenia, Uridine diphosphate glucoronosyltransferase 1A1",

author = "Wang Xi and Liu Ying and Huang Junxing and Lu Ping and Ba Yi and Wu Lin and Bai Yuxian and Zhang Shu and Feng Jifeng and Cheng Ying and Li Jie and Wen Lu and Yuan Xianglin and Ma Changwu and Hu Chunhong and Fan Qingxia and Xu Binghe and Huang Jing",

year = "2021",

month = nov,

day = "23",

doi = "10.3760/cma.j.cn112152-20191022-00678",

language = "繁体中文",

volume = "43",

pages = "1177--1182",

journal = "Zhonghua zhong liu za zhi [Chinese journal of oncology]",

issn = "0253-3766",

publisher = "Chinese Medical Journals Publishing House Co.Ltd",

number = "11",

}

Xi, W, Ying, L, Junxing, H, Ping, L, Yi, B, Lin, W, Yuxian, B, Shu, Z, Jifeng, F, Ying, C, Jie, L, Lu, W, Xianglin, Y, Changwu, M, Chunhong, H, Qingxia, F, Binghe, X & Jing, H 2021, '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', Zhonghua zhong liu za zhi [Chinese journal of oncology], vol. 43, no. 11, pp. 1177-1182. https://doi.org/10.3760/cma.j.cn112152-20191022-00678

TY - JOUR

T1 - 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

AU - Xi, Wang

AU - Ying, Liu

AU - Junxing, Huang

AU - Ping, Lu

AU - Yi, Ba

AU - Lin, Wu

AU - Yuxian, Bai

AU - Shu, Zhang

AU - Jifeng, Feng

AU - Ying, Cheng

AU - Jie, Li

AU - Lu, Wen

AU - Xianglin, Yuan

AU - Changwu, Ma

AU - Chunhong, Hu

AU - Qingxia, Fan

AU - Binghe, Xu

AU - Jing, Huang

PY - 2021/11/23

Y1 - 2021/11/23

N2 - 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/ m2) 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/ m2) 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.

AB - 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/ m2) 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/ m2) 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.

KW - Adverse events

KW - Diarrhea

KW - Esophageal squamous cell carcinoma

KW - Gene polymorphisms

KW - Irinotecan

KW - Neutropenia

KW - Uridine diphosphate glucoronosyltransferase 1A1

UR - https://www.scopus.com/pages/publications/85121993786

U2 - 10.3760/cma.j.cn112152-20191022-00678

DO - 10.3760/cma.j.cn112152-20191022-00678

M3 - 文章

C2 - 34794220

AN - SCOPUS:85121993786

SN - 0253-3766

VL - 43

SP - 1177

EP - 1182

JO - Zhonghua zhong liu za zhi [Chinese journal of oncology]

JF - Zhonghua zhong liu za zhi [Chinese journal of oncology]

IS - 11

ER -