PMID- 36971916
OWN - NLM
STAT- MEDLINE
DCOM- 20230424
LR  - 20230424
IS  - 1437-7772 (Electronic)
IS  - 1341-9625 (Linking)
VI  - 28
IP  - 5
DP  - 2023 May
TI  - Plasma trough concentration of imatinib and its effect on therapeutic efficacy 
      and adverse events in Japanese patients with GIST.
PG  - 680-687
LID - 10.1007/s10147-023-02325-x [doi]
AB  - BACKGROUND: Imatinib mesylate (IM) is the standard chemotherapy for patients with 
      gastrointestinal stromal tumors (GISTs) and has a favorable safety profile. 
      Pharmacokinetics (PK), such as plasma trough concentration (Cmin), varies among 
      patients, requiring the need for therapeutic drug monitoring (TDM) during IM 
      administration. Despite some reports from overseas, the relationship between 
      Cmin, adverse events (AEs), and treatment efficacy in Japanese patients with GIST 
      has still been lacking. This study aimed to investigate the relationship between 
      IM plasma concentration and AEs in Japanese patients with GISTs. METHODS: This 
      retrospective study analyzed the data of 83 patients who underwent IM treatment 
      for GISTs at our institution between May 2002 and September 2021. RESULTS: The IM 
      Cmin was associated with any grade of AEs (with AEs vs. without AEs = 1294 
      (260-4075) vs. 857 (163-1886) ng/mL, P < 0.001), edema (with edema vs. without 
      edema = 1278 (634-4075) vs. 1036 (163-4069) ng/mL, P = 0.017), and fatigue (with 
      fatigue vs. without fatigue = 1373 (634-4069) vs. 1046 (163-4075) ng/mL, 
      P = 0.044). Moreover, a Cmin >/= 1283 ng/mL was a risk factor for severe AEs. The 
      median progression-free survival (PFS) was 3.04 years in the lowest Cmin tertile 
      (T1, < 917 ng/mL) compared with 5.90 years for T2 and T3 (P = 0.010). CONCLUSION: 
      Edema and fatigue are potentially associated with IM plasma trough concentrations 
      of >/= 1283 ng/mL in Japanese patients with GISTs. Further, maintaining an IM 
      plasma trough concentration above 917 ng/mL may improve PFS.
CI  - (c) 2023. The Author(s) under exclusive licence to Japan Society of Clinical 
      Oncology.
FAU - Teranishi, Ryugo
AU  - Teranishi R
AD  - Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka 
      University, 2-2-E2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
FAU - Takahashi, Tsuyoshi
AU  - Takahashi T
AUID- ORCID: 0000-0003-2397-1478
AD  - Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka 
      University, 2-2-E2 Yamadaoka, Suita, Osaka, 565-0871, Japan. 
      ttakahashi2@gesurg.med.osaka-u.ac.jp.
FAU - Nishida, Toshirou
AU  - Nishida T
AD  - Department of Surgery, Japan Community Health Care Organization Osaka Hospital, 
      4-2-78, Fukushima, Fukushima-Ku, Osaka, Japan.
FAU - Kurokawa, Yukinori
AU  - Kurokawa Y
AD  - Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka 
      University, 2-2-E2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
FAU - Nakajima, Kiyokazu
AU  - Nakajima K
AD  - Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka 
      University, 2-2-E2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
FAU - Koh, Masahiro
AU  - Koh M
AD  - Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka 
      University, 2-2-E2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
FAU - Nishigaki, Takahiko
AU  - Nishigaki T
AD  - Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka 
      University, 2-2-E2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
FAU - Saito, Takuro
AU  - Saito T
AD  - Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka 
      University, 2-2-E2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
FAU - Yamamoto, Kazuyoshi
AU  - Yamamoto K
AD  - Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka 
      University, 2-2-E2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
FAU - Yamashita, Kotaro
AU  - Yamashita K
AD  - Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka 
      University, 2-2-E2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
FAU - Tanaka, Koji
AU  - Tanaka K
AD  - Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka 
      University, 2-2-E2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
FAU - Makino, Tomoki
AU  - Makino T
AD  - Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka 
      University, 2-2-E2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
FAU - Motoori, Masaaki
AU  - Motoori M
AD  - Department of Surgery, Osaka General Medical Center, 3-1-56, Bandai-Higashi, 
      Sumiyoshi-Ku, Osaka, Osaka, 558-8558, Japan.
FAU - Omori, Takeshi
AU  - Omori T
AD  - Department of Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, 
      Chuo-Ku, Osaka, Osaka, 541-8567, Japan.
FAU - Hirota, Seiichi
AU  - Hirota S
AD  - Department of Surgical Pathology, Hyogo Medical University School of Medicine, 
      1-1, Mugogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan.
FAU - Hayashi, Yoshito
AU  - Hayashi Y
AD  - Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka 
      University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
FAU - Takehara, Tetsuo
AU  - Takehara T
AD  - Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka 
      University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
FAU - Eguchi, Hidetoshi
AU  - Eguchi H
AD  - Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka 
      University, 2-2-E2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
FAU - Doki, Yuichiro
AU  - Doki Y
AD  - Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka 
      University, 2-2-E2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
LA  - eng
PT  - Journal Article
DEP - 20230327
PL  - Japan
TA  - Int J Clin Oncol
JT  - International journal of clinical oncology
JID - 9616295
RN  - 0 (Antineoplastic Agents)
RN  - 8A1O1M485B (Imatinib Mesylate)
SB  - IM
MH  - Humans
MH  - *Antineoplastic Agents/adverse effects/blood/therapeutic use
MH  - East Asian People
MH  - *Gastrointestinal Stromal Tumors/drug therapy/pathology
MH  - *Imatinib Mesylate/adverse effects/blood/therapeutic use
MH  - Retrospective Studies
MH  - *Drug Monitoring/methods
MH  - Treatment Outcome
MH  - Edema/chemically induced/etiology
MH  - Fatigue/chemically induced/etiology
OTO - NOTNLM
OT  - Adverse events
OT  - GIST
OT  - Imatinib
OT  - Plasma trough concentration
EDAT- 2023/03/28 06:00
MHDA- 2023/04/24 06:42
CRDT- 2023/03/27 11:19
PHST- 2022/12/07 00:00 [received]
PHST- 2023/03/01 00:00 [accepted]
PHST- 2023/04/24 06:42 [medline]
PHST- 2023/03/28 06:00 [pubmed]
PHST- 2023/03/27 11:19 [entrez]
AID - 10.1007/s10147-023-02325-x [pii]
AID - 10.1007/s10147-023-02325-x [doi]
PST - ppublish
SO  - Int J Clin Oncol. 2023 May;28(5):680-687. doi: 10.1007/s10147-023-02325-x. Epub 
      2023 Mar 27.