Exploratory randomized trial to evaluate the effect of indisetron tablets for preventing chemotherapy-induced nausea and vomiting (CINV)/acute-onset diarrhea induced by IRIS/FOLFIRI: HGCSG0704.

Abstract

624 Background: Indisetron is a 5-HT3 receptor antagonist that also antagonizes 5-HT4receptors. Indisetron tablets showed the non-inferiority to ondansetron tablets in terms of efficacy for preventing CINV. Moreover, preclinical data administered with irinotecan showed indisetron significantly reduced stool frequency in mice and inhibited the colonic peristalsis in dogs. We designed a pilot study compared with granisetron in the efficacy and tolerability of indisetron for irinotecan-induced nausea, vomiting and especially in diarrhea. Methods: Advanced colorectal cancer patients treated with FOLFIRI or IRIS (Irinotecan + S-1) with or without bevacizumab were enrolled in this study. Treatment: Arm A: indisetron tablets 8mg po day1. Arm B: granisetron 3mg iv day 1. The primary endpoints were the incidence of acute-onset diarrhea and complete protection from vomiting. Secondary endpoints were tolerability, complete protection from nausea and rate of no rescue medication. Results: Between May 2008 and July 2012, 33 patients (pts) were randomized. The study was closed prematurely due to poor accrual. Arm A: 16 pts, arm B 17 pts. Median age A: 68 y.o., B: 66 y.o.: ECOG PS 0/1: A: 12/4, B: 14/3pts. There was no significant difference of the incidence of acute-onset diarrhea between both groups (18.8% in A vs. 35.3% in B, p = 0.438). The proportion of complete protection from vomiting was 87.5% in A and 88.2% in B (p = 1.000). Similarly, complete protection from nausea, rate of no rescue medication, proportion of patients with a complete response (defined as no emetic episodes and no rescue medication) did not have a significant difference. Severity of nausea/vomiting and AE induced by 5-HT3 receptor antagonist were also similar between two groups. Conclusions: Compared with granisetron, indisetron showed effective and feasible results for preventing CINV induced by FOLFIRI or IRIS. Indisetron had also not improved the incidence of acute-onset diarrhea induced by irinotecan. Clinical trial information: UMIN000010162.