title: Antacid Use and De Novo Brain Metastases in Patients with Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer Who Were Treated Using First-Line First-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors.
abstract: BACKGROUND
  Antacid treatments decrease the serum concentrations of first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), although it is unknown whether antacids affect clinical outcomes. As cerebrospinal fluid concentrations of TKIs are much lower than serum concentrations, we hypothesized that this drug-drug interaction might affect the prognosis of patients with de novo brain metastases.
  
  
  METHODS
  This retrospective study evaluated 269 patients with EGFR-mutant non-small cell lung cancer (NSCLC) who had been diagnosed between December 2010 and December 2013, and had been treated using first-line first-generation EGFR-TKIs. Among these patients, we identified patients who concurrently used H2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) as antacids. Patients who exhibited >30% overlap between the use of TKIs and antacids were considered antacid users.
  
  
  RESULTS
  Fifty-seven patients (57/269, 21.2%) were antacid users, and antacid use did not significantly affect progression-free survival (PFS; no antacids: 11.2 months, H2RAs: 9.4 months, PPIs: 6.7 months; p = 0.234). However, antacid use significantly reduced overall survival (OS; no antacids: 25.0 months, H2RAs: 15.5 months, PPIs: 11.3 months; p = 0.002). Antacid use did not affect PFS for various metastasis sites, although antacid users with de novo brain metastases exhibited significantly shorter OS, compared to non-users (11.8 vs. 16.3 months, respectively; p = 0.041). Antacid use did not significantly affect OS in patients with bone, liver, or pleural metastases.
  
  
  CONCLUSIONS
  Antacid use reduced OS among patients with EGFR-mutant NSCLC who were treated using first-line first-generation EGFR-TKIs, and especially among patients with de novo brain metastases.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Yu-Mu
authors.initials: YM
authors.lastname: Chen
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Chien-Hao
authors.initials: CH
authors.lastname: Lai
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Huang-Chih
authors.initials: HC
authors.lastname: Chang
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Tung-Ying
authors.initials: TY
authors.lastname: Chao
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Chia-Cheng
authors.initials: CC
authors.lastname: Tseng
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.|Department of Respiratory Care, Chang Gung Institute of Technology, Chiayi, Taiwan.
authors.forename: Wen-Feng
authors.initials: WF
authors.lastname: Fang
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Chin-Chou
authors.initials: CC
authors.lastname: Wang
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Yu-Hsiu
authors.initials: YH
authors.lastname: Chung
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Yi-Hsi
authors.initials: YH
authors.lastname: Wang
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Mao-Chang
authors.initials: MC
authors.lastname: Su
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Shih-Feng
authors.initials: SF
authors.lastname: Liu
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Kuo-Tung
authors.initials: KT
authors.lastname: Huang
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Hung-Chen
authors.initials: HC
authors.lastname: Chen
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Ya-Chun
authors.initials: YC
authors.lastname: Chang
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Meng-Chih
authors.initials: MC
authors.lastname: Lin
mesh_terms: D000368:Aged; D000863:Antacids / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology*; D004347:Drug Interactions; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D012189:Retrospective Studies
chemical_list: D000863:Antacids; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors