Unexpected Side Effects of a High S-1 Dose: Subanalysis of a Phase III Trial Comparing Gemcitabine, S-1 and Combinatorial Treatments for Advanced Pancreatic Cancer

Oncology. 2016;91(3):117-26. doi: 10.1159/000446989. Epub 2016 Jun 16.

Abstract

Objective: In this subanalysis of a phase III trial using three categorized doses of S-1, the influence of the actual doses on safety and efficacy was evaluated.

Methods: We compared the efficacy and safety of the S-1 or gemcitabine plus S-1 combination (GS) arm between the top 10% group and the bottom 10% group according to the initial doses of S-1: ≥77.6 versus ≤65.9 mg/m2/day (n = 28 vs. 28) in the S-1 arm, and ≥65.1 versus ≤53.8 mg/m2/day (n = 27 vs. 28) in the GS arm.

Results: Overall and progression-free survival were not significantly different between these two groups: hazard ratios of 0.818 and 0.761 with p values of 0.498 and 0.330 in the S-1 arm, and hazard ratios of 0.836 and 0.759 with p values of 0.557 and 0.323 in the GS arm, respectively. Incidences of grade 3-4 hematological toxicities were significantly higher in the top 10% group than in the bottom 10% group: 42.9 versus 14.3 and 85.2 versus 57.1%, with p values of 0.037 and 0.037 in the S-1 and the GS combination arm, respectively.

Conclusions: Higher actual doses of S-1 were associated with a higher incidence of hematological toxicity even in the same dose setting.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Carcinoma, Adenosquamous / drug therapy*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Disease-Free Survival
  • Drug Combinations
  • Female
  • Gemcitabine
  • Hematologic Diseases / chemically induced
  • Humans
  • Male
  • Middle Aged
  • Oxonic Acid / administration & dosage
  • Oxonic Acid / adverse effects*
  • Pancreatic Neoplasms / drug therapy*
  • Retrospective Studies
  • Survival Rate
  • Tegafur / administration & dosage
  • Tegafur / adverse effects*

Substances

  • Drug Combinations
  • Deoxycytidine
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid
  • Gemcitabine