HGCSG 1301: A multicenter, double-blind, randomized controlled phase II trial comparing Hange-shashin-to versus placebo to prevent diarrhea in patients with metastatic colorectal cancer treated with IRIS/Bev as second-line therapy—Updated analysis of antitumor efficacy.
108 Background: IRIS (irinotecan plus S-1) plus bevacizumab (IRIS/Bev) is one of the standard chemotherapies in Japan for metastatic colorectal cancer (mCRC) as the first-line or second-line therapy. The most frequent non-hematological adverse event of IRIS was diarrhea. Hange-shashin-to (HST) is a Kampo medicine which is used in Japan for the treatment of gastritis, stomatitis, and diarrhea. We conducted this study to evaluate the usefulness of HST to prevent diarrhea in patients with mCRC receiving IRIS/Bev as the second-line therapy. Methods: This trial was designed as a multicenter, randomized, double-blind, placebo-controlled study. We administrated HST 2.5g or placebo PO t.i.d. x 3 months from the first treatment course of IRIS/Bev. The primary endpoint is proportion of ≥grade 3 diarrhea assessed by CTCAE v4.0. This study is registered with UMIN-CTR, number UMIN000012276. Results: Between Jan 1, 2014 and Mar 31, 2017, 59 patients from 11 institutes in Japan were randomly assigned to receive HST (n = 28, Group H) or placebo (n = 29, Group P). The proportions of ≥grade 3 diarrhea was 10.7% in Group H and 13.8% in Group P (p = 1.00). The other major adverse events of ≥grade 3 in Group H vs Group P were fatigue (3.6% vs 10.3%), anorexia (14.3% vs 10.3%), and nausea (0.0% vs 3.4%). The overall response rate was 13.6% in Group H vs 7.7% in Group P (p = 0.65). There were not statistically significant differences in median progression-free survival (mPFS), median time to treatment failure (mTTF), and median overall survival (mOS) between Group H and Group P ( mPFS 7.9 vs 5.9 months; p = 0.35; mTTF 3.8 vs 5.6; p = 0.466; mOS 17.0 vs 15.3 months; p = 0.750). Conclusions: Prophylactic HST could not reduce the severity of diarrhea during IRIS/Bev. The update analysis of anti-tumor efficacy showed that IRIS/Bev had promising survival benefit but there is not statistically significant difference between HST and placebo. Clinical trial information: UMIN000012276.