Please use this identifier to cite or link to this item: https://doi.org/10.18632/oncotarget.13458
Title: EGFR kinase inhibitors and gastric acid suppressants in EGFR-mutant NSCLC: A retrospective database analysis of potential drug interaction
Authors: Kumarakulasinghe, N.B
Syn, N
Soon, Y.Y
Asmat, A
Zheng, H
Loy, E.Y
Pang, B 
Soo, R.A 
Keywords: erlotinib
gefitinib
histamine H2 receptor antagonist
proton pump inhibitor
antineoplastic agent
EGFR protein, human
epidermal growth factor receptor
erlotinib
gefitinib
protein kinase inhibitor
proton pump inhibitor
quinazoline derivative
adult
aged
Article
cancer chemotherapy
Charlson Comorbidity Index
cohort analysis
controlled study
drug antagonism
drug use
EGFR gene
female
gene mutation
human
Karnofsky Performance Status
major clinical study
male
medical record review
non small cell lung cancer
overall survival
progression free survival
receptor gene
antagonists and inhibitors
chi square distribution
clinical trial
disease exacerbation
disease free survival
drug interaction
enzymology
factual database
genetics
Kaplan Meier method
lung tumor
metabolism
middle aged
mortality
multicenter study
multivariate analysis
mutation
non small cell lung cancer
proportional hazards model
retrospective study
risk assessment
risk factor
Singapore
time factor
treatment outcome
very elderly
Adult
Aged
Aged, 80 and over
Antineoplastic Agents
Carcinoma, Non-Small-Cell Lung
Chi-Square Distribution
Databases, Factual
Disease Progression
Disease-Free Survival
Drug Interactions
Erlotinib Hydrochloride
Female
Humans
Kaplan-Meier Estimate
Karnofsky Performance Status
Lung Neoplasms
Male
Middle Aged
Multivariate Analysis
Mutation
Proportional Hazards Models
Protein Kinase Inhibitors
Proton Pump Inhibitors
Quinazolines
Receptor, Epidermal Growth Factor
Retrospective Studies
Risk Assessment
Risk Factors
Singapore
Time Factors
Treatment Outcome
Issue Date: 2016
Publisher: Impact Journals LLC
Citation: Kumarakulasinghe, N.B, Syn, N, Soon, Y.Y, Asmat, A, Zheng, H, Loy, E.Y, Pang, B, Soo, R.A (2016). EGFR kinase inhibitors and gastric acid suppressants in EGFR-mutant NSCLC: A retrospective database analysis of potential drug interaction. Oncotarget 7 (51) : 85542-85550. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.13458
Abstract: Background: Erlotinib and gefitinib are weak base drugs whose absorption and clinical efficacy may be impaired by concomitant gastric acid suppressive (AS) therapy, yet proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2As) are widely indicated in non-small cell lung cancer (NSCLC) patients for the prevention and treatment of erlotinib-induced gastrointestinal injury and corticosteroid-associated gastric irritation. We assessed the clinical relevance of this potential drug-drug interaction (DDI) in a retrospective cohort of EGFR-mutant NSCLC patients. Results: The AS usage rate was 35%. In the overall cohort, AS users did not experience poorer OS (HR: 1.47, 95% CI: 0.92 - 2.35, P = 0.10; median, 11.4 versus 17.5 months) or PFS (HR = 1.37, 95% CI: 0.89 - 2.12, P = 0.16; median, 7.6 versus 8.7 months) compared with non-users in multivariate Cox regression analysis. However, subgroup analyses indicated that AS usage was associated with significantly poorer OS and PFS in patients who had fewer or milder comorbidities (Charlson comorbidity index ? 2), those with Karnofsky performance status < 90, and never-smokers. Materials and Methods: A retrospective database analysis of 157 patients given erlotinib or gefitinib for EGFR-mutant advanced NSCLC from two institutions was conducted. Patients were classified as AS-users if the periods of AS and anti-EGFR therapy overlapped by ? 30%. Overall survival (OS) and progression-free survival (PFS) were assessed according to AS usage. Conclusions: Concomitant AS therapy did not have an adverse impact on OS and/or PFS in the overall cohort. Our subgroup findings should be regarded exploratory and require replication in a large prospective cohort.
Source Title: Oncotarget
URI: https://scholarbank.nus.edu.sg/handle/10635/175449
ISSN: 19492553
DOI: 10.18632/oncotarget.13458
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