HGCSG1301 : A Multicenter, Double-Blind, Randomized control phase II trial comparing Hange-shashin-to versus placebo to prevent diarrhea in patient...

Date 24 November 2018
Event ESMO Asia 2018 Congress
Session Poster display - Cocktail
Topics Supportive Measures
Complications/Toxicities of Treatment
Colon and Rectal Cancer
Presenter Masayoshi Dazai
Citation Annals of Oncology (2018) 29 (suppl_9): ix28-ix45. 10.1093/annonc/mdy431
Authors M. Dazai1, S. Yuki2, K. Sawada3, T. Muranaka3, Y. Kawamoto2, H. Nakatsumi3, S. Nakano2, A. Ishiguro4, M. Tateyama5, A. Sato6, Y. Kobayashi7, M. Nakamura8, H. Okuda9, Y. Takahashi10, K. Eto11, S. Muto12, K. Hatanaka13, T. Amano14, Y. Sakata15, Y. Komatsu3
  • 1Gastroenterology, Sapporo Medical Center NTT EC, 060-0061 - Sapporo/JP
  • 2Gastroenterology And Hepatology, Hokkaido University Hospital, 060-8638 - Sapporo/JP
  • 3Cancer Center, Hokkaido University Hospital, 060-8638 - Sapporo/JP
  • 4Medical Oncology, Teine Keijinkai Hospital, 006-8555 - Sapporo/JP
  • 5Internal Medicine, Tomakomai Nisshou Hospital, Tomakomai/JP
  • 6Medical Oncology, Hirosaki University Graduate School of Medicine, Hirosaki/JP
  • 7Medical Oncology, Kushiro Rosai Hospital, 085-8533 - Kushiro/JP
  • 8Gastroenterology, Sapporo City General Hospital, 060-8604 - Sapporo/JP
  • 9Medical Oncology, Keiyukai Sapporo Hospital, 003-0027 - Sapporo/JP
  • 10Gastroenterology, Hokkaido Cancer Center, 003-0804 - Sapporo/JP
  • 11Gastroenterology, Tomakomai City Hospital, Tomakomai/JP
  • 12Gastroenterology, Hokkaido Medical Center, Sapporo/JP
  • 13Gastroenterology, Hakodate Municipal Hospital, 041-8680 - Hakodate/JP
  • 14Clinical Research And Medical Innovation Center, Hokkaido University Hospital, 060-8638 - Sapporo/JP
  • 15Ceo, Misawa City Hospital, 033-0022 - Misawa/JP



S-1 plus irinotecan (IRIS) was shown non-inferiority to fluorouracil and folinic acid plus irinotecan (FOLFIRI) by FIRIS study. Therefore IRIS is widely used with bevacizumab (IRIS/Bev) as the second-line chemotherapy in patients with colorectal cancer. The most frequent non-hematological adverse event shown at the study was diarrhea. Baicalin contained within hange-shashin-to is a potent competitive inhibitor of beta-glucuronidase which cleaves conjugated SN-38-glucuronide to SN-38 which causes cytotoxic diarrhea as an active metabolite from irinotecan. We conducted this trial to evaluate the usefulness of prophylactic administration of Hange-shashin-to to prevent diarrhea in patients receiving IRIS/Bev.


This trial was designed as a multicenter, randomized, double-blind, placebo-controlled study. We administrated Hange-shashin-to 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 or worse diarrhea assessed by CTCAE v4.0.


Between Jan 1, 2014 and Mar 31, 2017, 59 patients with colorectal cancer needing second-line chemotherapy from 11 institutes in Japan were randomly assigned to receive Hange-shashin-to (n = 28, Group H) or placebo (n = 29, Group P). The patients’ characteristics were well-balanced. The median relative dose intensities of S-1, irinotecan and bevacizumab were 0.89 vs 0.89, 0.89 vs 0.89 and 0.89 vs 0.86 in group H vs group P. The proportions of Grade 3 or worse diarrhea were 10.7% (3 of 28) in Group H and 13.8% (4 of 29) in Group P (p = 1.00). Those of any grade diarrhea were 64.3% (18 of 28 ) in Group H and 72.4% ( 21 of 29 ) in Group P (p = 0.58). The other major adverse events (grade 3 or worse) were fatigue (3.6% vs 10.3%), anorexia (14.3% vs 10.3%), nausea (0.0% vs 3.4%) in Group H vs Group P. The overall response rate in group H vs group P was 13.64% vs 7.69% (p = 0.65), and the disease control rate was 86.36% vs 80.8% (p = 0.71), respectively.


Our study to examine the diarrhea control effect by Hange-shashin-to induced by IRIS/Bev didn’t show any significant difference between two groups.

Editorial acknowledgement

Clinical trial identification

UMIN000012276, 2013/11/13.

Legal entity responsible for the study

Non-profit Organization: Hokkaido Gastrointestinal Cancer Study Group.


Non-profit Organization: Hokkaido Gastrointestinal Cancer Study Group.


S. Yuki: Honoraia: Chugai pharmaceutical Co., Ltd., Taiho pharmaceutical Co., Ltd. Y. Komatsu: Honoraria: Chugai, Taiho Donation: Chugai, Taiho Research fund: Taiho. All other authors have declared no conflicts of interest.