title: Gastric Acid suppression is associated with decreased erlotinib efficacy in non-small-cell lung cancer.
abstract: BACKGROUND
  Erlotinib is a key therapy for advanced NSCLC. Concurrent AS therapy with TKIs might reduce TKI plasma levels. Because of gastroesophageal reflux disease prevalence, this retrospective analysis was undertaken to determine if coadministering erlotinib with AS therapy affected NSCLC outcomes.
  
  
  METHODS
  Records of advanced NSCLC patients who received erlotinib from 2007 to 2012 at a large, centralized, cancer institution were retrospectively reviewed. Pertinent demographic data were collected and concomitant AS treatment was defined as AS prescription dates overlapping with ≥ 20% of erlotinib treatment duration. Records of patients who received erlotinib for ≥ 1 week were analyzed for progression-free survival (PFS) and overall survival (OS).
  
  
  RESULTS
  Stage IIIB/IV NSCLC patients (n = 544) were identified and 507 had adequate data for review. The median age was 64 years and 272 were female. Adenocarcinoma (n = 318; 64%) and squamous (n = 106; 21%) were predominant subtypes; 124 patients received concomitant AS therapy. In this unselected population, median PFS and OS in AS versus no AS groups were 1.4 versus 2.3 months (P < .001) and 12.9 versus 16.8 months (P = .003), respectively. Factoring sex, subtype, and performance status in multivariate Cox proportional hazards ratios for PFS and OS between AS and no AS groups were 1.83 (95% confidence interval [CI], 1.48-2.25) and 1.37 (95% CI, 1.11-1.69), respectively.
  
  
  CONCLUSIONS
  This large population-based study suggests erlotinib efficacy might be linked with gastric pH and OS could be adversely affected. To our knowledge, this is the first study demonstrating a possible negative clinical effect of coadministration of erlotinib with AS therapy. Further prospective investigation is warranted.
authors.affiliation: Department of Medical Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Chu
authors.affiliation: Department of Medical Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Sunita
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Department of Pharmacy, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Carole R
authors.initials: CR
authors.lastname: Chambers
authors.affiliation: Department of Medical Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Naveen
authors.initials: N
authors.lastname: Basappa
authors.affiliation: Department of Medical Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Butts
authors.affiliation: Department of Medical Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Quincy
authors.initials: Q
authors.lastname: Chu
authors.affiliation: Department of Medical Oncology, BC Cancer Agency, Vancouver Island Centre, Victoria, British Columbia, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Fenton
authors.affiliation: Department of Medical Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Anil A
authors.initials: AA
authors.lastname: Joy
authors.affiliation: Department of Medical Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Randeep
authors.initials: R
authors.lastname: Sangha
authors.affiliation: Department of Medical Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Smylie
authors.affiliation: Department of Medical Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada. Electronic address: michael.sawyer@albertahealthservices.ca.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Sawyer
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D004347:Drug Interactions; D000069347:Erlotinib Hydrochloride; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005764:Gastroesophageal Reflux / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006635:Histamine H2 Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008175:Lung Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000008:administration & dosage* / Q000009:adverse effects; D044382:Population Groups; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D006635:Histamine H2 Antagonists; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D009853:Omeprazole
keywords: Drug interactions; Erlotinib; Histamine type-2 receptor antagonist; Non-small cell lung cancer; Proton pump inhibitors