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摘要
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. ? 2021 Chinese Academy of Medical Sciences.
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