PMID- 37424405
OWN - NLM
STAT- MEDLINE
DCOM- 20231024
LR  - 20231024
IS  - 1752-8062 (Electronic)
IS  - 1752-8054 (Print)
IS  - 1752-8054 (Linking)
VI  - 16
IP  - 10
DP  - 2023 Oct
TI  - Associations of HLA-C*01:02 and HLA-B*46:01 with regorafenib-induced erythema 
      multiforme in Japanese patients with metastatic colorectal cancer.
PG  - 1741-1747
LID - 10.1111/cts.13589 [doi]
AB  - Regorafenib improves the survival of patients with metastatic colorectal cancer 
      (mCRC); however, it is also characterized by detrimental dermal side effects that 
      may require treatment cessation or modified dosing. In our previous prospective 
      pharmacokinetic, pharmacodynamic, and pharmacogenetic studies, 17.5% (7/40) of 
      the patients with mCRC had grade 3 erythema multiforme (EM) that caused treatment 
      discontinuation. Haplotypes in genes encoding human leukocyte antigen (HLA) are 
      associated with EM following the administration of drugs, such as allopurinol. 
      This study examined the association between HLA haplotypes and 
      regorafenib-induced EM. Regorafenib was administered orally at 160 mg/body once 
      daily for weeks 1-3 of each 4-week cycle. To determine the HLA haplotypes, we 
      used the WAKFlow HLA Typing Kit HLA-A, -B, or -C. The carrier frequency of 
      HLA-C*01:02 in patients with EM (6/7) was higher than that in tolerant controls 
      (8/33; odds ratio [OR] = 18.8, 95% confidence interval [CI] = 1.95-180, 
      p = 0.00437). HLA-B*46:01 was also associated with EM (OR = 11.6, 95% 
      CI = 1.47-92.1, p = 0.0299). These associations were no longer significant after 
      Bonferroni correction for multiple testing. Therefore, regorafenib-induced EM in 
      Japanese patients appears to be associated with specific HLA haplotypes but 
      further validation is needed.
CI  - (c) 2023 The Authors. Clinical and Translational Science published by Wiley 
      Periodicals LLC on behalf of American Society for Clinical Pharmacology and 
      Therapeutics.
FAU - Fujita, Ken-Ichi
AU  - Fujita KI
AUID- ORCID: 0000-0002-1575-6690
AD  - Division of Cancer Genome and Pharmacotherapy, Department of Clinical Pharmacy, 
      Showa University School of Pharmacy, Tokyo, Japan.
FAU - Matsumoto, Natsumi
AU  - Matsumoto N
AD  - Division of Cancer Genome and Pharmacotherapy, Department of Clinical Pharmacy, 
      Showa University School of Pharmacy, Tokyo, Japan.
FAU - Murase, Remi
AU  - Murase R
AD  - Division of Cancer Genome and Pharmacotherapy, Department of Clinical Pharmacy, 
      Showa University School of Pharmacy, Tokyo, Japan.
FAU - Takeshima, Kosuke
AU  - Takeshima K
AD  - Division of Cancer Genome and Pharmacotherapy, Department of Clinical Pharmacy, 
      Showa University School of Pharmacy, Tokyo, Japan.
FAU - Ishida, Hiroo
AU  - Ishida H
AD  - Division of Medical Oncology, Showa University Northern Yokohama Hospital, 
      Yokohama, Japan.
FAU - Kubota, Yutaro
AU  - Kubota Y
AD  - Division of Medical Oncology, Department of Medicine, Showa University School of 
      Medicine, Tokyo, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230719
PL  - United States
TA  - Clin Transl Sci
JT  - Clinical and translational science
JID - 101474067
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-C Antigens)
RN  - 24T2A1DOYB (regorafenib)
RN  - 0 (Antineoplastic Agents)
SB  - IM
MH  - Humans
MH  - *Colorectal Neoplasms/drug therapy/pathology
MH  - East Asian People
MH  - *Erythema Multiforme/chemically induced/genetics
MH  - HLA-B Antigens/genetics
MH  - HLA-C Antigens/genetics
MH  - *Antineoplastic Agents/adverse effects
PMC - PMC10582655
COIS- The authors declared no competing interests for this work.
EDAT- 2023/07/10 06:42
MHDA- 2023/10/23 00:42
PMCR- 2023/07/19
CRDT- 2023/07/10 04:03
PHST- 2023/06/26 00:00 [revised]
PHST- 2023/05/28 00:00 [received]
PHST- 2023/06/28 00:00 [accepted]
PHST- 2023/10/23 00:42 [medline]
PHST- 2023/07/10 06:42 [pubmed]
PHST- 2023/07/10 04:03 [entrez]
PHST- 2023/07/19 00:00 [pmc-release]
AID - CTS13589 [pii]
AID - 10.1111/cts.13589 [doi]
PST - ppublish
SO  - Clin Transl Sci. 2023 Oct;16(10):1741-1747. doi: 10.1111/cts.13589. Epub 2023 Jul 
      19.