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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 |
Appears in Collections: | Staff Publications Elements |
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