Abstract
Introduction: Cisplatin-based highly emetogenic chemotherapy is recommended in combination with neurokinin-1 receptor antagonist, 5-hydroxytryptamine-3-receptor antagonist (5HT3RA), dexamethasone (DEX), and olanzapine. However, olanzapine is contraindicated in patients with preexisting diabetes mellitus (DM). This study compared the efficacy of a triplet antiemetic regimen (NK1RA, 5HT3RA, and DEX) in patients with and without preexisting DM treated with cisplatin-based chemotherapy. Methods: This retrospective study enrolled patients with esophageal cancer with and without preexisting DM who received fluorouracil and cisplatin (FP) combination chemotherapy as initial therapy with a triplet antiemetic regimen for antiemetic prophylaxis. These data were compared using propensity score matching (PSM). The primary endpoint was the complete response (CR) rate during the first cycle, which was defined as no emetic episodes and no rescue medication use during the overall period (0–120 h). The CR rate was analyzed using univariate and multivariate logistic regression, including previously reported risk factors. The significance level was set at 5%. Results: Out of 210 eligible patients, 39 and 39 were patients with DM and non-DM patients after PSM, respectively. The CR rate measured by multivariate analysis during the overall period with DM and non-DM was 56.4% and 41.0% (adjusted odds ratio of 0.566 [95% confidence intervals: 0.209–1.536], p = 0.264), respectively. The CR rate during the delayed period (24–120 h) with DM and non-DM patients was 84.6% and 46.2% (p = 0.002), respectively. Conclusions: A triplet antiemetic regimen in patients with esophageal cancer with preexisting DM might be more effective in delayed period compared to non-DM patients.
Journal Section:
Clinical Study
References
1.
Aogi
K
, Takeuchi
H
, Saeki
T
, Aiba
K
, Tamura
K
, Iino
K
, et al. Optimizing antiemetic treatment for chemotherapy-induced nausea and vomiting in Japan: update summary of the 2015 Japan society of clinical Oncology clinical practice guidelines for antiemesis
. Int J Clin Oncol
. 2021
;26
(1
):1
–17
. 2.
Herrstedt
J
, Celio
L
, Hesketh
PJ
, Zhang
L
, Navari
R
, Chan
A
, et al. 2023 updated MASCC/ESMO consensus recommendations: prevention of nausea and vomiting following high-emetic-risk antineoplastic agents
. Support Care Cancer
. 2023
;32
(1
):47
. 3.
SEER NCI Cancer stat facts: esophageal cancer
[cited 2024 Aug 7]. Available from: https://seer.cancer.gov/statfacts/html/esoph.html#:∼:text=Rate%20of%20New%20Cases%20and%20Deaths%20per4.
Ishiguro
S
, Sasazuki
S
, Inoue
M
, Kurahashi
N
, Iwasaki
M
, Tsugane
S
, et al. Effect of alcohol consumption, cigarette smoking and flushing response on esophageal cancer risk: a population-based cohort study (JPHC study)
. Cancer Lett
. 2009
;275
(2
):240
–6
. 5.
Sakata
K
, Hoshiyama
Y
, Morioka
S
, Hashimoto
T
, Takeshita
T
, Tamakoshi
A
, et al. Smoking, alcohol drinking and esophageal cancer: findings from the JACC Study
. J Epidemiol
. 2005
;15 Suppl 2
(Suppl II
):S212
–9
. 6.
Secretan
B
, Straif
K
, Baan
R
, Grosse
Y
, El Ghissassi
F
, Bouvard
V
, et al. A review of human carcinogens--Part E: tobacco, areca nut, alcohol, coal smoke, and salted fish
. Lancet Oncol
. 2009
;10
(11
):1033
–4
. 7.
Steevens
J
, Schouten
LJ
, Goldbohm
RA
, van den Brandt
PA
. Alcohol consumption, cigarette smoking and risk of subtypes of oesophageal and gastric cancer: a prospective cohort study
. Gut
. 2010
;59
(1
):39
–48
. 8.
Willi
C
, Bodenmann
P
, Ghali
WA
, Faris
PD
, Cornuz
J
. Active smoking and the risk of type 2 diabetes: a systematic review and meta-analysis
. JAMA
. 2007
;298
(22
):2654
–64
. 9.
Edwards
BK
, Noone
AM
, Mariotto
AB
, Simard
EP
, Boscoe
FP
, Henley
SJ
, et al. Annual Report to the Nation on the status of cancer, 1975-2010, featuring prevalence of comorbidity and impact on survival among persons with lung, colorectal, breast, or prostate cancer
. Cancer
. 2014
;120
(9
):1290
–314
. 10.
Renehan
A
, Smith
U
, Kirkman
MS
. Linking diabetes and cancer: a consensus on complexity
. Lancet
. 2010
;375
(9733
):2201
–2
. 11.
Ando
N
, Kato
H
, Igaki
H
, Shinoda
M
, Ozawa
S
, Shimizu
H
, et al. A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907)
. Ann Surg Oncol
. 2012
;19
(1
):68
–74
. 12.
Hayashi
K
, Ando
N
, Watanabe
H
, Ide
H
, Nagai
K
, Aoyama
N
, et al. Phase II evaluation of protracted infusion of cisplatin and 5-fluorouracil in advanced squamous cell carcinoma of the esophagus: a Japan Esophageal Oncology Group (JEOG) Trial (JCOG9407)
. Jpn J Clin Oncol
. 2001
;31
(9
):419
–23
. 13.
The label approved by FDA, Reference ID: 4596612
[cited 2024 December 20] Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020592s074,021086s048,021253s061lbl.pdf#page=3714.
Takemura
M
, Ikemura
K
, Kondo
M
, Yamane
F
, Ueda
M
, Okuda
M
. Concomitant palonosetron ameliorates cisplatin-induced nephrotoxicity, nausea, and vomiting: a retrospective cohort study and pharmacovigilance analysis
. J Pharm Health Care Sci
. 2022
;8
(1
):21
. 15.
Tsuji
D
, Suzuki
K
, Kawasaki
Y
, Goto
K
, Matsui
R
, Seki
N
, et al. Risk factors associated with chemotherapy-induced nausea and vomiting in the triplet antiemetic regimen including palonosetron or granisetron for cisplatin-based chemotherapy: analysis of a randomized, double-blind controlled trial
. Support Care Cancer
. 2019
;27
(3
):1139
–47
. 16.
Global
BMIMC
, Di Angelantonio
E
, Bhupathiraju
SN
, Wormser
D
, Gao
P
, Kaptoge
S
, et al. Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents
. Lancet
. 2016
;388
(10046
):776
–86
. 17.
Prospective Studies Collaboration
, Whitlock
G
, Lewington
S
, Sherliker
P
, Clarke
R
, Emberson
J
, et al. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies
. Lancet
. 2009
;373
(9669
):1083
–96
. 18.
Hepsen
S
, Sencar
E
, Sakiz
D
, Akhanli
P
, Ucan
B
, Unsal
I
, et al. Serum cortisol level after low dose dexamethasone suppression test may be predictive for diabetes mellitus and hypertension presence in obese patients: a retrospective study
. Diabetes Res Clin Pract
. 2020
;161
:108081
. 19.
Hudson
JI
, Hudson
MS
, Rothschild
AJ
, Vignati
L
, Schatzberg
AF
, Melby
JC
. Abnormal results of dexamethasone suppression tests in nondepressed patients with diabetes mellitus
. Arch Gen Psychiatry
. 1984
;41
(11
):1086
–9
. 20.
Mistrova
E
, Kruzliak
P
, Chottova Dvorakova
M
. Role of substance P in the cardiovascular system
. Neuropeptides
. 2016
;58
:41
–51
. 21.
Kunt
T
, Forst
T
, Schmidt
S
, Pfützner
A
, Schneider
S
, Harzer
O
, et al. Serum levels of substance P are decreased in patients with type 1 diabetes
. Exp Clin Endocrinol Diabetes
. 2000
;108
(3
):164
–7
. 22.
Takahashi
T
, Nakamura
Y
, Tsuya
A
, Murakami
H
, Endo
M
, Yamamoto
N
. Pharmacokinetics of aprepitant and dexamethasone after administration of chemotherapeutic agents and effects of plasma substance P concentration on chemotherapy-induced nausea and vomiting in Japanese cancer patients
. Cancer Chemother Pharmacol
. 2011
;68
(3
):653
–9
. 23.
Park
HS
, Won
HS
, An
HJ
, Cho
SS
, Kim
HH
, Sun
S
, et al. Elevated serum substance P level as a predictive marker for moderately emetogenic chemotherapy-induced nausea and vomiting: a prospective cohort study
. Cancer Med
. 2021
;10
(3
):1057
–65
. 24.
Hashimoto
H
, Abe
M
, Tokuyama
O
, Mizutani
H
, Uchitomi
Y
, Yamaguchi
T
, et al. Olanzapine 5 mg plus standard antiemetic therapy for the prevention of chemotherapy-induced nausea and vomiting (J-FORCE): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial
. Lancet Oncol
. 2020
;21
(2
):242
–9
. 25.
Takahashi
T
, Hoshi
E
, Takagi
M
, Katsumata
N
, Kawahara
M
, Eguchi
K
. Multicenter, phase II, placebo-controlled, double-blind, randomized study of aprepitant in Japanese patients receiving high-dose cisplatin
. Cancer Sci
. 2010
;101
(11
):2455
–61
. 26.
Aydın
B
, Özçelik
S
, Kilit
TP
, Eraslan
S
, Çelik
M
, Onbaşı
K
. Relationship between glycosylated hemoglobin and iron deficiency anemia: a common but overlooked problem
. Prim Care Diabetes
. 2022
;16
(2
):312
–7
. 27.
28.
Iorgulescu
JB
, Gokhale
PC
, Speranza
MC
, Eschle
BK
, Poitras
MJ
, Wilkens
MK
, et al. Concurrent dexamethasone limits the clinical benefit of immune checkpoint blockade in glioblastoma
. Clin Cancer Res
. 2021
;27
(1
):276
–87
. 29.
Janowitz
T
, Kleeman
S
, Vonderheide
RH
. Reconsidering dexamethasone for antiemesis when combining chemotherapy and immunotherapy
. Oncologist
. 2021
;26
(4
):269
–73
. 30.
Tokunaga
A
, Sugiyama
D
, Maeda
Y
, Warner
AB
, Panageas
KS
, Ito
S
, et al. Selective inhibition of low-affinity memory CD8(+) T cells by corticosteroids
. J Exp Med
. 2019
;216
(12
):2701
–13
. 31.
Nakamura
M
, Ishiguro
A
, Muranaka
T
, Fukushima
H
, Yuki
S
, Ono
K
, et al. A prospective observational study on effect of short-term periodic steroid premedication on bone metabolism in gastrointestinal cancer (ESPRESSO-01)
. Oncologist
. 2017
;22
(5
):592
–600
. 32.
Ito
Y
, Tsuda
T
, Minatogawa
H
, Kano
S
, Sakamaki
K
, Ando
M
, et al. Placebo-Controlled, double-blinded phase III study comparing dexamethasone on day 1 with dexamethasone on days 1 to 3 with combined neurokinin-1 receptor antagonist and palonosetron in high-emetogenic chemotherapy
. J Clin Oncol
. 2018
;36
(10
):1000
–6
. 33.
Minatogawa
H
, Izawa
N
, Shimomura
K
, Arioka
H
, Iihara
H
, Sugawara
M
, et al. Dexamethasone-sparing on days 2-4 with combined palonosetron, neurokinin-1 receptor antagonist, and olanzapine in cisplatin: a randomized phase III trial (SPARED Trial)
. Br J Cancer
. 2024
;130
(2
):224
–32
. 34.
Celio
L
, Bartsch
R
, Aapro
M
. Dexamethasone-sparing regimens with NEPA (netupitant/palonosetron) for the prevention of chemotherapy-induced nausea and vomiting in older patients (>65 years) fit for cisplatin: a sub-analysis from a phase 3 study
. J Geriatr Oncol
. 2023
;14
(6
):101537
. 35.
Nyman
MJ
, Eskola
O
, Kajander
J
, Vahlberg
T
, Sanabria
S
, Burns
D
, et al. Gender and age affect NK1 receptors in the human brain: a positron emission tomography study with [18F]SPA-RQ
. Int J Neuropsychopharmacol
. 2007
;10
(2
):219
–29
. © 2024 S. Karger AG, Basel
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
2024
You do not currently have access to this content.
