Abstract
Introduction: Antihistamines (AHs) have beneficial effects as adjuvant anticancer agent in several preclinical and observational studies. We aimed to evaluate the effect of AHs on stage IV lung cancer patients. Methods: We used data from the Cancer Registry Database provided by the Cancer Center of Kaohsiung Veterans General Hospital to investigate whether AH use is associated with improved survival among patients with stage IV lung cancer. We analyzed AHs use across various patient subgroups, including sex, age, comorbidities, co-medications, smoking status, histologic type, treatment modality, and survival time. The primary endpoint was overall survival (OS). Results: A total of 1,886 lung cancer patients were enrolled. Of them, 41 (2.1%) patients were AH users, 1,845 (97.8%) were AH nonusers before lung cancer diagnosis, and 594 (31.6%) patients were AH users, 1,292 (68.4%) were AH nonusers after lung cancer diagnosis. AH users were more to have comorbidities with hypertension (p < 0.001), diabetes mellitus (p < 0.001), allergic disease (p < 0.001), chronic obstructive pulmonary disease (p = 0.002), co-medications with targeted therapy (p < 0.001), and nonaspirin NSAID (p < 0.001). Pre-diagnostic AH users did not show improved survival outcomes. Post-diagnostic AH users tend to have a better OS among patients with a survival period of more than 90 days (median, 28.4 months and 15.1 months, respectively; HR: 0.49; 95% confidence interval: 0.43–0.55). Conclusion: AHs use was associated with improved OS in patients with stage IV lung cancer. Further prospective studies are needed to better elucidate the role of AHs in the treatment of lung cancer.
Journal Section:
Clinical Study
References
1.
Branco
ACCC
, Yoshikawa
FSY
, Pietrobon
AJ
, Sato
MN
. Role of histamine in modulating the immune response and inflammation
. Mediators Inflamm
. 2018
;2018
:9524075
. 2.
Faustino-Rocha
AI
, Ferreira
R
, Gama
A
, Oliveira
PA
, Ginja
M
. Antihistamines as promising drugs in cancer therapy
. Life Sci
. 2017
;172
:27
–41
. 3.
de Guadalupe Chávez-López
M
, Hernández-Gallegos
E
, Vázquez-Sánchez
AY
, Gariglio
P
, Camacho
J
. Antiproliferative and proapoptotic effects of astemizole on cervical cancer cells
. Int J Gynecol Cancer
. 2014
;24
(5
):824
–8
. 4.
Chávez-López
MDG
, Zúñiga-García
V
, Hernández-Gallegos
E
, Vera
E
, Chasiquiza-Anchatuña
CA
, Viteri-Yánez
M
, et al. The combination astemizole-gefitinib as a potential therapy for human lung cancer
. Onco Targets Ther
. 2017
;10
:5795
–803
. 5.
Fritz
I
, Wagner
P
, Olsson
H
. Improved survival in several cancers with use of H1-antihistamines desloratadine and loratadine
. Transl Oncol
. 2021
;14
(4
):101029
. 6.
Bens
A
, Dehlendorff
C
, Friis
S
, Cronin-Fenton
D
, Jensen
MB
, Ejlertsen
B
, et al. The role of H1 antihistamines in contralateral breast cancer: a Danish nationwide cohort study
. Br J Cancer
. 2020
;122
(7
):1102
–8
. 7.
Verdoodt
F
, Dehlendorff
C
, Jäättelä
M
, Strauss
R
, Pottegård
A
, Hallas
J
, et al. Antihistamines and ovarian cancer survival: nationwide cohort study and in vitro cell viability assay
. J Natl Cancer Inst
. 2020
;112
(9
):964
–7
. 8.
Shen
Y-C
, Hsu
H-C
, Lin
T-M
, Chang
Y-S
, Hu
L-F
, Chen
L-F
, et al. H1-Antihistamines reduce the risk of hepatocellular carcinoma in patients with hepatitis B virus, hepatitis C virus, or dual hepatitis B virus-hepatitis C virus infection
. J Clin Oncol
. 2022
;40
(11
):1206
–19
. 9.
Chang
C-L
, Lin
K-C
, Chen
W-M
, Shia
B-C
, Wu
S-Y
. Antihistamines H1 use on survival outcomes in esophageal squamous cell carcinoma patients undergoing concurrent chemoradiotherapy
. Am J Cancer Res
. 2023
;13
(11
):5733
–45
.10.
Chiang
C-H
, Chiang
C-H
, Hsia
YP
, Chen
BS
, Jaroenlapnopparat
A
, Chiang
C-H
, et al. The efficacy of cationic amphiphilic antihistamines on outcomes of patients with pancreatic ductal adenocarcinoma
. J Gastrointest Cancer
. 2024
;55
(1
):175
–7
. 11.
Siegel
RL
, Giaquinto
AN
, Jemal
A
. Cancer statistics, 2024
. CA Cancer J Clin
. 2024
;74
(1
):12
–49
. Erratum in: CA Cancer J Clin. 2024;74(2):203. 12.
Incidence and mortality rates for the top 10 cancer in Taiwan
; 2021
. Available from:
https://twcr.tw/?page_id=1855&lang=en13.
Kuo
CN
, Liao
YM
, Kuo
LN
, Tsai
HJ
, Chang
WC
, Yen
Y
. Cancers in Taiwan: practical insight from epidemiology, treatments, biomarkers, and cost
. J Formos Med Assoc
. 2020
;119
(12
):1731
–41
. 14.
Rami-Porta
R
, Nishimura
KK
, Giroux
DJ
, Detterbeck
F
, Cardillo
G
, Edwards
JG
, et al. The international association for the study of lung cancer lung cancer staging project: proposals for revision of the TNM stage groups in the forthcoming (ninth) edition of the TNM classification for lung cancer
. J Thorac Oncol
. 2024
;19
(7
):1007
–27
. 15.
Kratzer
TB
, Bandi
P
, Freedman
ND
, Smith
RA
, Travis
WD
, Jemal
A
, et al. Lung cancer statistics, 2023
. Cancer
. 2024
;130
(8
):1330
–48
. 16.
Chang
Y-J
, Huang
J-Y
, Lin
C-H
, Wang
B-Y
. Survival and treatment of lung cancer in Taiwan between 2010 and 2016
. J Clin Med
. 2021
;10
(20
):4675
. 17.
Goldstraw
P
, Chansky
K
, Crowley
J
, Rami-Porta
R
, Asamura
H
, Eberhardt
WEE
, et al. The IASLC lung cancer staging project: proposals for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for lung cancer
. J Thorac Oncol
. 2016
;11
(1
):39
–51
. 18.
Reck
M
, Remon
J
, Hellmann
MD
. First-line immunotherapy for non-small-cell lung cancer
. J Clin Oncol
. 2022
;40
(6
):586
–97
. Erratum in: J Clin Oncol. 2022;40(11):1265. 19.
Chiang
C-J
, You
S-L
, Chen
C-J
, Yang
Y-W
, Lo
W-C
, Lai
M-S
. Quality assessment and improvement of nationwide cancer registration system in Taiwan: a review
. Jpn J Clin Oncol
. 2015
;45
(3
):291
–6
. 20.
Mok
TS
, Wu
Y-L
, Thongprasert
S
, Yang
C-H
, Chu
D-T
, Saijo
N
, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma
. N Engl J Med
. 2009
;361
(10
):947
–57
. 21.
Goto
K
, Nishio
M
, Yamamoto
N
, Chikamori
K
, Hida
T
, Maemondo
M
, et al. A prospective, phase II, open-label study (JO22903) of first-line erlotinib in Japanese patients with epidermal growth factor receptor (EGFR) mutation-positive advanced non-small-cell lung cancer (NSCLC)
. Lung Cancer
. 2013
;82
(1
):109
–14
. 22.
Seto
T
, Kato
T
, Nishio
M
, Goto
K
, Atagi
S
, Hosomi
Y
, et al. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study
. Lancet Oncol
. 2014
;15
(11
):1236
–44
. Erratum in: Lancet Oncol. 2014;15(11):e475. 23.
Kato
T
, Yoshioka
H
, Okamoto
I
, Yokoyama
A
, Hida
T
, Seto
T
, et al. Afatinib versus cisplatin plus pemetrexed in Japanese patients with advanced non-small cell lung cancer harboring activating EGFR mutations: subgroup analysis of LUX-Lung 3
. Cancer Sci
. 2015
;106
(9
):1202
–11
. 24.
Sequist
LV
, Yang
JC
, Yamamoto
N
, O’Byrne
K
, Hirsh
V
, Mok
T
, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations
. J Clin Oncol
. 2013
;31
(27
):3327
–34
. 25.
Califano
R
, Tariq
N
, Compton
S
, Fitzgerald
DA
, Harwood
CA
, Lal
R
, et al. Expert consensus on the management of adverse events from EGFR tyrosine kinase inhibitors in the UK
. Drugs
. 2015
;75
(12
):1335
–48
. 26.
Chu
CY
, Chen
KY
, Wen-Cheng Chang
J
, Wei
YF
, Lee
CH
, Wang
WM
. Taiwanese Dermatological Association consensus for the prevention and management of epidermal growth factor receptor tyrosine kinase inhibitor-related skin toxicities
. J Formos Med Assoc
. 2017
;116
(6
):413
–23
. 27.
Kris
MG
, Natale
RB
, Herbst
RS
, Lynch
TJ
Jr, Prager
D
, Belani
CP
, et al. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial
. JAMA
. 2003
;290
(16
):2149
–58
. 28.
Mohamed
MK
, Ramalingam
S
, Lin
Y
, Gooding
W
, Belani
CP
. Skin rash and good performance status predict improved survival with gefitinib in patients with advanced non-small cell lung cancer
. Ann Oncol
. 2005
;16
(5
):780
–5
. 29.
Wacker
B
, Nagrani
T
, Weinberg
J
, Witt
K
, Clark
G
, Cagnoni
PJ
. Correlation between development of rash and efficacy in patients treated with the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in two large phase III studies
. Clin Cancer Res
. 2007
;13
(13
):3913
–21
. 30.
Ellegaard
A-M
, Dehlendorff
C
, Vind
AC
, Anand
A
, Cederkvist
L
, Petersen
NHT
, et al. Repurposing cationic amphiphilic antihistamines for cancer treatment
. EBioMedicine
. 2016
;9
:130
–9
. 31.
Zhao
J
, Hou
Y
, Yin
C
, Hu
J
, Gao
T
, Huang
X
, et al. Upregulation of histamine receptor H1 promotes tumor progression and contributes to poor prognosis in hepatocellular carcinoma
. Oncogene
. 2020
;39
(8
):1724
–38
. 32.
Hernández-Angeles
A
, Soria-Jasso
LE
, Ortega
A
, Arias-Montaño
JA
. Histamine H1 receptor activation stimulates mitogenesis in human astrocytoma U373 MG cells
. J Neuro Oncol
. 2001
;55
(2
):81
–9
. 33.
Davio
C
, Baldi
A
, Mladovan
A
, Cricco
G
, Fitzsimons
C
, Bergoc
R
, et al. Expression of histamine receptors in different cell lines derived from mammary gland and human breast carcinomas
. Inflamm Res
. 1995
;44
(Suppl 1
):S70
–1
. 34.
Li
H
, Xiao
Y
, Li
Q
, Yao
J
, Yuan
X
, Zhang
Y
, et al. The allergy mediator histamine confers resistance to immunotherapy in cancer patients via activation of the macrophage histamine receptor H1
. Cancer Cell
. 2022
;40
(1
):36
–52.e9
. 35.
Eylemer Mocan
E
, Yekedüz
E
, Karataş
G
, Yazgan
SC
, Köksoy
EB
, Çay Şenler
F
, et al. Impact of antihistamine use on the survival outcomes of immune checkpoint inhibitors in advanced cancer patients
. Anticancer Drugs
. 2024
;35
(2
):190
–4
. 36.
Liu
X
, Zhong
R
, Huang
J
, Chen
Z
, Xu
H
, Lin
L
, et al. Loratidine is associated with improved prognosis and exerts antineoplastic effects via apoptotic and pyroptotic crosstalk in lung cancer
. J Exp Clin Cancer Res
. 2024
;43
(1
):5
. 37.
Zhang
S
, Zhao
L
, Guo
M
, Liu
P
, Li
S
, Xie
W
, et al. Anticancer effects of ikarugamycin and astemizole identified in a screen for stimulators of cellular immune responses
. J Immunother Cancer
. 2023
;11
(7
):e006785
. 38.
Mok
TS
, Wu
Y-L
, Ahn
M-J
, Garassino
MC
, Kim
HR
, Ramalingam
SS
, et al. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer
. N Engl J Med
. 2017
;376
(7
):629
–40
. 39.
Hochmair
MJ
, Morabito
A
, Hao
D
, Yang
CT
, Soo
RA
, Yang
JCH
, et al. Sequential afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer: final analysis of the GioTag study
. Future Oncol
. 2020
;16
(34
):2799
–808
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