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Prospective study of the UGT1A1*27 gene polymorphism during irinotecan therapy in patients with lung cancer: Results of Lung Oncology Group in Kyusyu (LOGIK1004B)

BACKGROUND: Uridine 5′‐diphospho‐glucuronosyltransferase 1A1 (UGT1A1*27) is known to impair the effect of UGT in basic research; however, little clinical investigation has been conducted. To evaluate the effect of the UGT1A1*27 polymorphism in irinotecan therapy, we conducted a prospective study. ME...

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Autores principales: Fukuda, Minoru, Suetsugu, Takayuki, Shimada, Midori, Kitazaki, Takeshi, Hashiguchi, Kohji, Kishimoto, Junji, Harada, Taishi, Seto, Takashi, Ebi, Noriyuki, Takayama, Koichi, Sugio, Kenji, Semba, Hiroshi, Nakanishi, Yoichi, Ichinose, Yukito
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons Australia, Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4930967/
https://www.ncbi.nlm.nih.gov/pubmed/27385990
http://dx.doi.org/10.1111/1759-7714.12360
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author Fukuda, Minoru
Suetsugu, Takayuki
Shimada, Midori
Kitazaki, Takeshi
Hashiguchi, Kohji
Kishimoto, Junji
Harada, Taishi
Seto, Takashi
Ebi, Noriyuki
Takayama, Koichi
Sugio, Kenji
Semba, Hiroshi
Nakanishi, Yoichi
Ichinose, Yukito
author_facet Fukuda, Minoru
Suetsugu, Takayuki
Shimada, Midori
Kitazaki, Takeshi
Hashiguchi, Kohji
Kishimoto, Junji
Harada, Taishi
Seto, Takashi
Ebi, Noriyuki
Takayama, Koichi
Sugio, Kenji
Semba, Hiroshi
Nakanishi, Yoichi
Ichinose, Yukito
author_sort Fukuda, Minoru
collection PubMed
description BACKGROUND: Uridine 5′‐diphospho‐glucuronosyltransferase 1A1 (UGT1A1*27) is known to impair the effect of UGT in basic research; however, little clinical investigation has been conducted. To evaluate the effect of the UGT1A1*27 polymorphism in irinotecan therapy, we conducted a prospective study. METHODS: Eligibility criteria included: lung cancer patients; scheduled irinotecan therapy doses of single ≥ 80, combination ≥ 50, radiation with single ≥ 50, or radiation with combination ≥ 40 mg/m(2); age ≥ 20; and Eastern Cooperative Oncology Group performance score (PS) 0–2. Patients were examined for UGT1A1*28 and *6 polymorphisms and received irinotecan. When the UGT1A1*28 polymorphism was detected, a search for UGT1A1*27 was conducted. Fifty patients were enrolled, with 48 patients determined eligible. RESULTS: UGT1A1 polymorphisms *28/*28, *6/*6, *28/*6, *28/−, *6/−, −/− observed 0 (0%), 1 (2%), 1 (2%), 7 (15%), 17 (35%) and 22 (46%), respectively. UGT1A1*27 were examined in nine patients including one ineligible patient; however, no polymorphisms were found. The study ceased after interim analysis. In an evaluation of the side effects of irinotecan, patients with UGT1A1*28 and UGT1A1*6 polymorphisms had a higher tendency to experience febrile neutropenia than wild type (25% and 32% vs. 14%). Incidences of grade 3/4 leukopenia and neutropenia were significantly higher in patients with UGT1A1*28 polymorphisms compared with wild type (75% vs. 32%, P = 0.049; 75% vs. 36%, P = 0.039, respectively). CONCLUSION: Our prospective study did not locate the UGT1A1*27 polymorphism, suggesting that UGT1A1*27 does not significantly predict severe irinotecan toxicity in cancer patients.
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spelling pubmed-49309672016-07-06 Prospective study of the UGT1A1*27 gene polymorphism during irinotecan therapy in patients with lung cancer: Results of Lung Oncology Group in Kyusyu (LOGIK1004B) Fukuda, Minoru Suetsugu, Takayuki Shimada, Midori Kitazaki, Takeshi Hashiguchi, Kohji Kishimoto, Junji Harada, Taishi Seto, Takashi Ebi, Noriyuki Takayama, Koichi Sugio, Kenji Semba, Hiroshi Nakanishi, Yoichi Ichinose, Yukito Thorac Cancer Original Articles BACKGROUND: Uridine 5′‐diphospho‐glucuronosyltransferase 1A1 (UGT1A1*27) is known to impair the effect of UGT in basic research; however, little clinical investigation has been conducted. To evaluate the effect of the UGT1A1*27 polymorphism in irinotecan therapy, we conducted a prospective study. METHODS: Eligibility criteria included: lung cancer patients; scheduled irinotecan therapy doses of single ≥ 80, combination ≥ 50, radiation with single ≥ 50, or radiation with combination ≥ 40 mg/m(2); age ≥ 20; and Eastern Cooperative Oncology Group performance score (PS) 0–2. Patients were examined for UGT1A1*28 and *6 polymorphisms and received irinotecan. When the UGT1A1*28 polymorphism was detected, a search for UGT1A1*27 was conducted. Fifty patients were enrolled, with 48 patients determined eligible. RESULTS: UGT1A1 polymorphisms *28/*28, *6/*6, *28/*6, *28/−, *6/−, −/− observed 0 (0%), 1 (2%), 1 (2%), 7 (15%), 17 (35%) and 22 (46%), respectively. UGT1A1*27 were examined in nine patients including one ineligible patient; however, no polymorphisms were found. The study ceased after interim analysis. In an evaluation of the side effects of irinotecan, patients with UGT1A1*28 and UGT1A1*6 polymorphisms had a higher tendency to experience febrile neutropenia than wild type (25% and 32% vs. 14%). Incidences of grade 3/4 leukopenia and neutropenia were significantly higher in patients with UGT1A1*28 polymorphisms compared with wild type (75% vs. 32%, P = 0.049; 75% vs. 36%, P = 0.039, respectively). CONCLUSION: Our prospective study did not locate the UGT1A1*27 polymorphism, suggesting that UGT1A1*27 does not significantly predict severe irinotecan toxicity in cancer patients. John Wiley & Sons Australia, Ltd 2016-05-11 2016-07 /pmc/articles/PMC4930967/ /pubmed/27385990 http://dx.doi.org/10.1111/1759-7714.12360 Text en © 2016 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Fukuda, Minoru
Suetsugu, Takayuki
Shimada, Midori
Kitazaki, Takeshi
Hashiguchi, Kohji
Kishimoto, Junji
Harada, Taishi
Seto, Takashi
Ebi, Noriyuki
Takayama, Koichi
Sugio, Kenji
Semba, Hiroshi
Nakanishi, Yoichi
Ichinose, Yukito
Prospective study of the UGT1A1*27 gene polymorphism during irinotecan therapy in patients with lung cancer: Results of Lung Oncology Group in Kyusyu (LOGIK1004B)
title Prospective study of the UGT1A1*27 gene polymorphism during irinotecan therapy in patients with lung cancer: Results of Lung Oncology Group in Kyusyu (LOGIK1004B)
title_full Prospective study of the UGT1A1*27 gene polymorphism during irinotecan therapy in patients with lung cancer: Results of Lung Oncology Group in Kyusyu (LOGIK1004B)
title_fullStr Prospective study of the UGT1A1*27 gene polymorphism during irinotecan therapy in patients with lung cancer: Results of Lung Oncology Group in Kyusyu (LOGIK1004B)
title_full_unstemmed Prospective study of the UGT1A1*27 gene polymorphism during irinotecan therapy in patients with lung cancer: Results of Lung Oncology Group in Kyusyu (LOGIK1004B)
title_short Prospective study of the UGT1A1*27 gene polymorphism during irinotecan therapy in patients with lung cancer: Results of Lung Oncology Group in Kyusyu (LOGIK1004B)
title_sort prospective study of the ugt1a1*27 gene polymorphism during irinotecan therapy in patients with lung cancer: results of lung oncology group in kyusyu (logik1004b)
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4930967/
https://www.ncbi.nlm.nih.gov/pubmed/27385990
http://dx.doi.org/10.1111/1759-7714.12360
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