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

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.

Design, synthesis, and biological evaluation of novel <strong>EF24 </strong>and <strong>EF31 </strong>analogs as potential I&kappa;B kinase &beta; inhibitors for the treatment of pancreatic cancer

“…Currently, various combination therapeutic regimens have been assessed in clinical or preclinical practice in the hope of overcoming the intricate mechanism of resistance 11,12. Unfortunately, this approach is also more likely to increase the incidence of toxic effects, such as irreversible myelosuppression and gastrointestinal adverse reactions 13. Thus, development of new targeted therapies for PC is highly urgent and crucial.…”