title: An evaluation of the possible interaction of gastric acid suppressing medication and the EGFR tyrosine kinase inhibitor erlotinib.
abstract: OBJECTIVE
  As the bioavailability of erlotinib is dependent on gastric pH, an increase in gastric pH via the concurrent use of gastric acid suppressive medications (AS) may reduce its bioavailability and efficacy. We retrospectively analyzed the BR.21 trial database to pragmatically evaluate the impact of AS use on the median plasma drug levels of erlotinib, adverse events and outcome of participants.
  
  
  METHODS
  Monthly median plasma levels of erlotinib were compared between participants utilizing AS and those who did not using a Wilcoxon test. Interaction p-value for AS users and AS non-users was performed using a multivariate Cox model with a time-dependent covariate for AS use. Grade 2 adverse events were compared using Fisher's Exact Test.
  
  
  RESULTS
  The median plasma erlotinib level was not significantly different between AS users and AS non-users, and AS use did not appear to incur a negative impact on PFS or OS (Interaction p-values: PFS p = 0.16; OS p = 0.81). AS users receiving erlotinib had a similar frequency of rash (50.5% vs. 42.0%, p = 0.08) and a statistically higher rate of diarrhea (27.9% vs. 15.6%, p = 0.001) compared to AS non-users. In addition, AS users had higher rates of infections (erlotinib arm: 33.7% vs. 20.0%, p < 0.0001; placebo arm: 22.7% vs. 10.8%, p = 0.02).
  
  
  CONCLUSIONS
  This retrospective analysis found that the co-administration of AS and erlotinib did not appear to have a significant impact on the median plasma drug levels or outcome.
authors.affiliation: NCIC Clinical Trials Group, Queens University, 10 Stuart Street, Kingston, Ontario, Canada K7L-3N6.
authors.forename: J F
authors.initials: JF
authors.lastname: Hilton
authors.forename: D
authors.initials: D
authors.lastname: Tu
authors.forename: L
authors.initials: L
authors.lastname: Seymour
authors.forename: F A
authors.initials: FA
authors.lastname: Shepherd
authors.forename: P A
authors.initials: PA
authors.lastname: Bradbury
mesh_terms: D000897:Anti-Ulcer Agents / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004347:Drug Interactions; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000494:pharmacology* / Q000627:therapeutic use; D054328:Proton Pump Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011799:Quinazolines / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D011899:Ranitidine / Q000494:pharmacology / Q000627:therapeutic use; D012189:Retrospective Studies; D013276:Stomach Ulcer / Q000188:drug therapy; D016896:Treatment Outcome
chemical_list: D000897:Anti-Ulcer Agents; D000970:Antineoplastic Agents; D054328:Proton Pump Inhibitors; D011799:Quinazolines; D011899:Ranitidine; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D009853:Omeprazole
keywords: Bioavailability; Drug–drug interactions; Erlotinib; H2-receptor antagonist; Pharmacokinetics; Proton pump inhibitors