PMID- 32666389
OWN - NLM
STAT- MEDLINE
DCOM- 20201125
LR  - 20231104
IS  - 1437-7772 (Electronic)
IS  - 1341-9625 (Print)
IS  - 1341-9625 (Linking)
VI  - 25
IP  - 10
DP  - 2020 Oct
TI  - 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.
PG  - 1800-1806
LID - 10.1007/s10147-020-01720-y [doi]
AB  - 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.
FAU - Nakano, Shintaro
AU  - Nakano S
AD  - Department of Gastroenterology and Hepatology, Hokkaido University Hospital, 
      Kita14, Nishi5, Kita-Ku, Sapporo, Hokkaido, 060-8648, Japan.
FAU - Yuki, Satoshi
AU  - Yuki S
AD  - Department of Gastroenterology and Hepatology, Hokkaido University Hospital, 
      Kita14, Nishi5, Kita-Ku, Sapporo, Hokkaido, 060-8648, Japan.
FAU - Kawamoto, Yasuyuki
AU  - Kawamoto Y
AD  - Department of Gastroenterology and Hepatology, Hokkaido University Hospital, 
      Kita14, Nishi5, Kita-Ku, Sapporo, Hokkaido, 060-8648, Japan.
FAU - Nakatsumi, Hiroshi
AU  - Nakatsumi H
AD  - Division of Cancer Center, Hokkaido University Hospital, Kita14, Nishi5, Kita-Ku, 
      Sapporo, Hokkaido, 060-8648, Japan.
FAU - Ando, Takayuki
AU  - Ando T
AD  - Department of Gastroenterology and Hematology, Faculty of Medicine, University of 
      Toyama, 2630, Sugitani, Toyama-shi, Toyama, 930-0194, Japan.
FAU - Kajiura, Shinya
AU  - Kajiura S
AD  - Department of Gastroenterology and Hematology, Faculty of Medicine, University of 
      Toyama, 2630, Sugitani, Toyama-shi, Toyama, 930-0194, Japan.
FAU - Yoshikawa, Ayumu
AU  - Yoshikawa A
AD  - Department of Medical Oncology, Kushiro Rosai Hospital, 13-23 Nakazono-cho, 
      Kushiro, Hokkaido, 085-8533, Japan.
FAU - Harada, Kazuaki
AU  - Harada K
AD  - Department of Medical Oncology, Kushiro Rosai Hospital, 13-23 Nakazono-cho, 
      Kushiro, Hokkaido, 085-8533, Japan.
FAU - Hatanaka, Kazuteru
AU  - Hatanaka K
AD  - Department of Gastroenterology, Hakodate Municipal Hospital, 1-10-1 Minatomachi, 
      Hakodate, Hokkaido, 041-8680, Japan.
FAU - Tanimoto, Aya
AU  - Tanimoto A
AD  - Department of Medical Oncology, Teine Keijinkai Hospital, 1-40, Maeda1-12, 
      Teine-Ku, Sapporo, Hokkaido, 006-8555, Japan.
FAU - Ishiguro, Atsushi
AU  - Ishiguro A
AD  - Department of Medical Oncology, Teine Keijinkai Hospital, 1-40, Maeda1-12, 
      Teine-Ku, Sapporo, Hokkaido, 006-8555, Japan.
FAU - Honda, Takuya
AU  - Honda T
AD  - Division of Clinical Oncology Center, Nagasaki University Hospital, 1-7-1, 
      Sakamoto, Nagasaki, 852-8501, Japan.
FAU - Dazai, Masayoshi
AU  - Dazai M
AD  - Department of Gastroenterology, Sapporo Medical Center NTT EC, Minami1, Nishi5, 
      Chuo-Ku, Sapporo, Hokkaido, 060-0061, Japan.
FAU - Sasaki, Takahide
AU  - Sasaki T
AD  - Department of Internal Medicine, Hokkaido Gastroenterology Hospital, 2-10, 
      Honcho1-1, Higashi-Ku, Sapporo, Hokkaido, 065-0041, Japan.
FAU - Sakamoto, Naoya
AU  - Sakamoto N
AD  - Department of Gastroenterology and Hepatology, Hokkaido University Hospital, 
      Kita14, Nishi5, Kita-Ku, Sapporo, Hokkaido, 060-8648, Japan.
FAU - Komatsu, Yoshito
AU  - Komatsu Y
AUID- ORCID: 0000-0002-1570-6802
AD  - Division of Cancer Center, Hokkaido University Hospital, Kita14, Nishi5, Kita-Ku, 
      Sapporo, Hokkaido, 060-8648, Japan. ykomatsu@ac.cyberhome.ne.jp.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
DEP - 20200714
PL  - Japan
TA  - Int J Clin Oncol
JT  - International journal of clinical oncology
JID - 9616295
RN  - 0 (Platinum Compounds)
RN  - 0 (Pyrimidines)
RN  - 675-21-8 (5-fluoropyrimidine)
RN  - 7673326042 (Irinotecan)
RN  - EC 2.4.1.- (UGT1A1 enzyme)
RN  - EC 2.4.1.17 (Glucuronosyltransferase)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Female
MH  - Glucuronosyltransferase/*genetics
MH  - Heterozygote
MH  - Humans
MH  - Irinotecan/adverse effects/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Platinum Compounds/administration & dosage
MH  - Pyrimidines/administration & dosage/*therapeutic use
MH  - Retrospective Studies
MH  - Stomach Neoplasms/*drug therapy/genetics/mortality
MH  - Treatment Outcome
MH  - Young Adult
PMC - PMC7498487
OTO - NOTNLM
OT  - Gastric cancer
OT  - Irinotecan
OT  - UGT1A1
COIS- Yoshito Komatsu has received honoraria from Taiho, Yakult, and Daichi-Sankyo and 
      research grants from Taiho, Yakult, and Daichi-Sankyo. All remaining authors 
      declare that they have no conflict of interest.
EDAT- 2020/07/16 06:00
MHDA- 2020/11/26 06:00
PMCR- 2020/07/14
CRDT- 2020/07/16 06:00
PHST- 2020/03/16 00:00 [received]
PHST- 2020/06/02 00:00 [accepted]
PHST- 2020/07/16 06:00 [pubmed]
PHST- 2020/11/26 06:00 [medline]
PHST- 2020/07/16 06:00 [entrez]
PHST- 2020/07/14 00:00 [pmc-release]
AID - 10.1007/s10147-020-01720-y [pii]
AID - 1720 [pii]
AID - 10.1007/s10147-020-01720-y [doi]
PST - ppublish
SO  - Int J Clin Oncol. 2020 Oct;25(10):1800-1806. doi: 10.1007/s10147-020-01720-y. 
      Epub 2020 Jul 14.