内容紹介
Examination of UGT1A1 Polymorphisms and Irinotecan-Induced Neutropenia in Patients with Colorectal Cancer
Summary
Irinotecan is an effective drug in the treatment of colorectal cancer. However, there are reports of an association between certain UGT1A1 genetic polymorphisms and the development of adverse reactions(such as neutropenia)related to irinotecan metabolism. We retrospectively investigated UGT1A1 genetic polymorphisms and the occurrences of irinotecan-induced neutropenia in 25 patients of colorectal cancer at our hospital. Analysis of UGT1A1 genetic polymorphisms in these patients yielded the following classifications: a wild-type group(*1/*1)comprising 13 patients(52%), a heterozygous group(*1/*28, *1/*6)of 10 patients(40%), and a homozygous group(*28/*28, *6/*6)of 2 patients(8%). The frequency of neutropenia was 15.4%(2/13)in the wild-type group, 30%(3/10)in the heterozygous group, and 100%(2/2)in the homozygous group. Grade 4 neutropenia only occurred in the homozygous group. These results suggest that a dose reduction of irinotecan should be considered for patients who fall into the homozygous group upon analysis of their UGT1A1 genetic polymorphisms, as such patients might be susceptible to grade 4 neutropenia.
要旨
イリノテカン(CPT-11)は大腸癌治療において有効な薬剤である。一方,CPT-11による好中球減少とその代謝酵素であるUGT1A1遺伝子多型の関連性が報告されている。今回,当院における大腸癌25例においてCPT-11の有害事象と,UGT1A1遺伝子多型について後方視的に検討した。UGT1A1遺伝子多型解析では,ワイルド群(*1/*1)52%(13/25),ヘテロ群(*1/*28,*1/*6)40%(10/25),ホモ群(*28/*28,*6/*6)が8%(2/25)の頻度であった。好中球減少は,ワイルド群15.4%(2/13),ヘテロ群(*28ヘテロ型や*6ヘテロ型)30%(3/10),ホモ群(*28ホモ型や*6ホモ型)で100%(2/2)の頻度であった。grade 4の発熱性好中球数減少はホモ群でのみ認めた。今回の結果よりホモ群では重篤な好中球減少を招く可能性があり,UGT1A1遺伝子検査実施の上でCPT-11の減量も考慮すべきと思われた。
目次
Summary
Irinotecan is an effective drug in the treatment of colorectal cancer. However, there are reports of an association between certain UGT1A1 genetic polymorphisms and the development of adverse reactions(such as neutropenia)related to irinotecan metabolism. We retrospectively investigated UGT1A1 genetic polymorphisms and the occurrences of irinotecan-induced neutropenia in 25 patients of colorectal cancer at our hospital. Analysis of UGT1A1 genetic polymorphisms in these patients yielded the following classifications: a wild-type group(*1/*1)comprising 13 patients(52%), a heterozygous group(*1/*28, *1/*6)of 10 patients(40%), and a homozygous group(*28/*28, *6/*6)of 2 patients(8%). The frequency of neutropenia was 15.4%(2/13)in the wild-type group, 30%(3/10)in the heterozygous group, and 100%(2/2)in the homozygous group. Grade 4 neutropenia only occurred in the homozygous group. These results suggest that a dose reduction of irinotecan should be considered for patients who fall into the homozygous group upon analysis of their UGT1A1 genetic polymorphisms, as such patients might be susceptible to grade 4 neutropenia.
要旨
イリノテカン(CPT-11)は大腸癌治療において有効な薬剤である。一方,CPT-11による好中球減少とその代謝酵素であるUGT1A1遺伝子多型の関連性が報告されている。今回,当院における大腸癌25例においてCPT-11の有害事象と,UGT1A1遺伝子多型について後方視的に検討した。UGT1A1遺伝子多型解析では,ワイルド群(*1/*1)52%(13/25),ヘテロ群(*1/*28,*1/*6)40%(10/25),ホモ群(*28/*28,*6/*6)が8%(2/25)の頻度であった。好中球減少は,ワイルド群15.4%(2/13),ヘテロ群(*28ヘテロ型や*6ヘテロ型)30%(3/10),ホモ群(*28ホモ型や*6ホモ型)で100%(2/2)の頻度であった。grade 4の発熱性好中球数減少はホモ群でのみ認めた。今回の結果よりホモ群では重篤な好中球減少を招く可能性があり,UGT1A1遺伝子検査実施の上でCPT-11の減量も考慮すべきと思われた。