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Impact of single-heterozygous UGT1A1 on the clinical outcomes of irinotecan monotherapy after fluoropyrimidine and platinum-based combination therapy for gastric cancer : a multicenter retrospective study

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Title: Impact of single-heterozygous UGT1A1 on the clinical outcomes of irinotecan monotherapy after fluoropyrimidine and platinum-based combination therapy for gastric cancer : a multicenter retrospective study
Authors: Nakano, Shintaro Browse this author
Yuki, Satoshi Browse this author
Kawamoto, Yasuyuki Browse this author →KAKEN DB
Nakatsumi, Hiroshi Browse this author →KAKEN DB
Ando, Takayuki Browse this author
Kajiura, Shinya Browse this author →KAKEN DB
Yoshikawa, Ayumu Browse this author
Harada, Kazuaki Browse this author
Hatanaka, Kazuteru Browse this author
Tanimoto, Aya Browse this author
Ishiguro, Atsushi Browse this author
Honda, Takuya Browse this author
Dazai, Masayoshi Browse this author
Sasaki, Takahide Browse this author
Sakamoto, Naoya Browse this author →KAKEN DB
Komatsu, Yoshito Browse this author →KAKEN DB
Keywords: Gastric cancer
Irinotecan
Issue Date: Oct-2021
Publisher: Springer
Journal Title: International journal of clinical oncology
Volume: 25
Start Page: 1800
End Page: 1806
Publisher DOI: 10.1007/s10147-020-01720-y
Abstract: Background It is unclear whether the UGT1A1 status, single heterozygous (SH) or wild type (WT), is associated with the efficacy and toxicity of irinotecan monotherapy in advanced gastric cancer (AGC). We investigated the association between clinical outcomes (efficacy and safety) and UGT1A1 status in patients who received irinotecan monotherapy. Methods We evaluated AGC patients who received irinotecan monotherapy between January 2011 and December 2017. Efficacy was assessed according to overall survival (OS) and progression-free survival (PFS). Toxicity was graded using the Common Toxicity Criteria for Adverse Events (version 4.0). Results A total of 100 patients were evaluated (62 and 38 patients with UGT1A1 WT and SH, respectively). In the WT and SH groups, the irinotecan dose was reduced in 19 (30.6%) and 18 (47.2%) patients (p = 0.135), respectively; treatment was delayed due to adverse events (AEs) in 19 (30.6%) and 13 (34.2%) patients (p = 0.826), respectively; the median PFS was 3.15 and 3.25 months (HR, 0.734; 95% CI 0.465-1.158;p = 0.184), respectively; and the median OS was 10.4 and 7.26 months (HR, 1.137; 95% CI 0.752-1.721;p = 0.543), respectively. Severe hematological AEs (Grade >= 3) were significantly more frequent in the SH group than in the WT group (63% vs. 36%;p = 0.008), while severe non-hematological AEs was not significantly different (16.0% vs. 6.5%;p = 0.173). Conclusion There was no significant difference in the efficacy of irinotecan monotherapy between UGT1A1 WT and UGT1A1 SH, but UGT1A1 SH was associated with a high frequency of severe hematological toxicity.
Rights: http://creativecommons.org/licenses/by/4.0/
Type: article
URI: http://hdl.handle.net/2115/79364
Appears in Collections:北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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