Reduction in gastrointestinal toxicity by gastric secretion inhibitors during S-1 monotherapy for patients with gastric cancer

Biol Pharm Bull. 2014;37(7):1158-61. doi: 10.1248/bpb.b14-00025.


The purpose of this study was to retrospectively examine the effect of concomitant administration of gastric secretion inhibitors or gastrectomy on the frequency of gastrointestinal toxicity caused by 5-fluorouracil (5-FU) in gastric cancer patients receiving chemotherapy with S-1. In 62 gastric cancer patients treated with S-1 alone, data relating to the occurrence of gastrointestinal toxicity (diarrhea, vomiting, and nausea) and possible contributing factors were retrospectively collected, and logistic regression analysis was performed. Time-to-event data relating to the occurrence of gastrointestinal toxicity were also collected, and the effect of gastric secretion inhibitors on the time-to-event profiles was examined using a log-rank test. Logistic regression analysis suggested that the frequency of gastrointestinal toxicity was significantly reduced by the administration of gastric secretion inhibitors (p=0.01; odds ratio, 0.197; 95% confidence interval (CI), 0.056-0.694) and that gastrointestinal toxicity correlated with the estimated glomerular filtration rate (p=0.04; odds ratio, 0.956; 95% CI, 0.916-0.997). The median time-to-event of gastrointestinal toxicity was 85 d for patients that received gastric secretion inhibitors, which was significantly different from the 42 d for patients that did not receive the inhibitors (p=0.02, log-rank test). No clear effect of gastrectomy was found in the present study. The prophylactic use of gastric secretion inhibitors in gastric cancer patients treated with S-1 may decrease and delay the occurrence of gastrointestinal toxicity.

MeSH terms

  • Aged
  • Diarrhea / chemically induced
  • Diarrhea / prevention & control
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Female
  • Gastric Mucosa* / drug effects
  • Gastric Mucosa* / metabolism
  • Histamine H2 Antagonists / administration & dosage
  • Histamine H2 Antagonists / therapeutic use*
  • Humans
  • Kaplan-Meier Estimate
  • Logistic Models
  • Male
  • Middle Aged
  • Nausea / chemically induced
  • Nausea / prevention & control
  • Oxonic Acid / administration & dosage
  • Oxonic Acid / adverse effects*
  • Oxonic Acid / therapeutic use
  • Proton Pump Inhibitors / administration & dosage
  • Proton Pump Inhibitors / therapeutic use*
  • Retrospective Studies
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / surgery
  • Tegafur / administration & dosage
  • Tegafur / adverse effects*
  • Tegafur / therapeutic use
  • Vomiting / chemically induced
  • Vomiting / prevention & control


  • Drug Combinations
  • Histamine H2 Antagonists
  • Proton Pump Inhibitors
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid