PMID- 35488047
OWN - NLM
STAT- MEDLINE
DCOM- 20220503
LR  - 20220716
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 12
IP  - 1
DP  - 2022 Apr 29
TI  - Proton pump inhibitors reduce the survival of advanced lung cancer patients with 
      therapy of gefitinib or erlotinib.
PG  - 7002
LID - 10.1038/s41598-022-10938-x [doi]
LID - 7002
AB  - Gefitinib and erlotinib are the first-line tyrosine kinase inhibitors (TKI) for 
      advanced non-small-cell lung cancer. However, co-administration of either drug 
      with proton pump inhibitors (PPI) or histamine-2 receptor antagonists (H2RA) may 
      reduce TKI's bioavailability. Therefore, we aimed to investigate the effects of 
      these drug-drug interactions. We surveyed nationwide population-based databases 
      between Jan 1, 2010, and Dec 30, 2018. Newly diagnosed patients with advanced 
      lung adenocarcinoma who received first-line gefitinib or erlotinib were 
      identified. Effects on overall survival (OS) and time to next treatment (TTNT) 
      association between PPIs or H2RAs and co-administrated gefitinib or erlotinib 
      were evaluated. PPIs or H2RAs users were defined if the period overlapped with 
      TKIs by >/= 20%. A total of 4340 gefitinib and 1635 erlotinib users were included. 
      PPI group had the shortest median OS and TTNT compared to the H2RA and non-user 
      groups (in gefitinib cohort: OS: 14.35 vs. 17.67 vs. 21.87 months; P < 0.0001, 
      TTNT: 8.47 vs. 10.78 vs. 10.33 months; P < 0.0001); (in erlotinib cohort: OS: 
      16.97 vs. 20.07 vs. 23.92 months; P < 0.0001, TTNT: 9.06 vs. 11.85 vs. 
      10.90 months; P = 0.0808). Compared with the non-user group, the adjusted hazard 
      ratio (aHR) of the PPI group in the gefitinib was 1.58 on OS (95% CI 1.42-1.76), 
      1.37 on TTNT (95% CI 1.24-1.52); in the erlotinib was 1.54 on OS (95% CI 
      1.30-1.82) and 1.19 on TTNT (95% CI 1.01-1.39). Concurrent use of PPIs with 
      first-line gefitinib or erlotinib therapy was associated with a worse OS and TTNT 
      in patients with lung adenocarcinoma harboring EGFR mutations.
CI  - (c) 2022. The Author(s).
FAU - Lee, Chia-Han
AU  - Lee CH
AD  - School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, 100, 
      Shih-Chuan 1st Road, Kaohsiung, 807, Taiwan.
FAU - Shen, Mei-Chiou
AU  - Shen MC
AUID- ORCID: 0000-0003-1977-2871
AD  - Department of Pharmacy, Kaohsiung Medical University Hospital, Kaohsiung Medical 
      University, Kaohsiung, Taiwan.
FAU - Tsai, Ming-Ju
AU  - Tsai MJ
AUID- ORCID: 0000-0003-3621-3334
AD  - Division of Pulmonary and Critical Care Medicine, Department of Internal 
      Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 
      Kaohsiung, Taiwan.
AD  - Department of Internal Medicine, School of Medicine, College of Medicine, 
      Kaohsiung Medical University, Kaohsiung, Taiwan.
FAU - Chang, Jung-San
AU  - Chang JS
AUID- ORCID: 0000-0002-9797-4885
AD  - Doctoral Degree Program in Toxicology, College of Pharmacy, Kaohsiung Medical 
      University, Kaohsiung, Taiwan.
AD  - Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical 
      University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
FAU - Huang, Yaw-Bin
AU  - Huang YB
AUID- ORCID: 0000-0002-6024-0108
AD  - School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, 100, 
      Shih-Chuan 1st Road, Kaohsiung, 807, Taiwan.
AD  - Department of Pharmacy, Kaohsiung Medical University Hospital, Kaohsiung Medical 
      University, Kaohsiung, Taiwan.
FAU - Yang, Yi-Hsin
AU  - Yang YH
AUID- ORCID: 0000-0002-9581-2778
AD  - School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, 100, 
      Shih-Chuan 1st Road, Kaohsiung, 807, Taiwan.
AD  - National Institute of Cancer Research, National Health Research Institutes, 
      Tainan, Taiwan.
FAU - Hsieh, Kun-Pin
AU  - Hsieh KP
AUID- ORCID: 0000-0003-1565-2936
AD  - School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, 100, 
      Shih-Chuan 1st Road, Kaohsiung, 807, Taiwan. kphsieh@kmu.edu.tw.
AD  - Department of Pharmacy, Kaohsiung Medical University Hospital, Kaohsiung Medical 
      University, Kaohsiung, Taiwan. kphsieh@kmu.edu.tw.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220429
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Histamine H2 Antagonists)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Proton Pump Inhibitors)
RN  - 0 (Quinazolines)
RN  - DA87705X9K (Erlotinib Hydrochloride)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - S65743JHBS (Gefitinib)
SB  - IM
MH  - *Adenocarcinoma of Lung/chemically induced/drug therapy
MH  - *Carcinoma, Non-Small-Cell Lung/pathology
MH  - ErbB Receptors
MH  - Erlotinib Hydrochloride
MH  - Gefitinib/therapeutic use
MH  - Histamine H2 Antagonists/therapeutic use
MH  - Humans
MH  - *Lung Neoplasms/pathology
MH  - Protein Kinase Inhibitors
MH  - Proton Pump Inhibitors/therapeutic use
MH  - Quinazolines
PMC - PMC9054789
COIS- The authors declare no competing interests.
EDAT- 2022/04/30 06:00
MHDA- 2022/05/04 06:00
PMCR- 2022/04/29
CRDT- 2022/04/29 23:24
PHST- 2021/05/20 00:00 [received]
PHST- 2022/04/12 00:00 [accepted]
PHST- 2022/04/29 23:24 [entrez]
PHST- 2022/04/30 06:00 [pubmed]
PHST- 2022/05/04 06:00 [medline]
PHST- 2022/04/29 00:00 [pmc-release]
AID - 10.1038/s41598-022-10938-x [pii]
AID - 10938 [pii]
AID - 10.1038/s41598-022-10938-x [doi]
PST - epublish
SO  - Sci Rep. 2022 Apr 29;12(1):7002. doi: 10.1038/s41598-022-10938-x.