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Effect of TU-100, a traditional Japanese medicine, administered after hepatic resection in patients with liver cancer: a multi-center, phase III trial (JFMC40-1001)

International Journal of Clinical Oncology volume 20, pages 95–104 (2015)Cite this article

Abstract

Background

This multi-center, phase III trial assesses the efficacy of daikenchuto (TU-100) on gastrointestinal disorders after hepatic resection (UMIN Registration No. 000003103).

Materials and methods

A total of 231 patients, who underwent hepatic resection at 26 Japanese centers, were enrolled. Patients were randomly assigned to receive either oral doses (15 g/day, three times a day) of TU-100 or placebo control from preoperative day 3 to postoperative day 10, except on the day of surgery. Primary end points were the time from extubation until the first postoperative bowel movement (FBM-T), serum C-reactive protein (CRP) and ammonia levels.

Results

Finally, 209 patients (TU-100: n = 108, placebo: n = 101) were included in the statistical analysis. The median FBM-T was 88.2 h (95 % CI 74.0–94.1) in the TU-100 group and 93.1 h (95 % CI 83.3–99.4) in the placebo group, demonstrating that TU-100 accelerated the time to first bowel movement significantly more than placebo control. Serum CRP levels did not differ significantly during the study period, although serum CRP levels in the TU-100 group tended to be lower than those in the placebo group in patients with grade B liver damage. Meanwhile, the two groups had similar serum ammonia levels. TU-100-related serious adverse events did not occur during the study.

Conclusions

TU-100 appears to improve gastrointestinal dysmotility and reduce serum CRP levels in patients with grade B liver damage after hepatectomy. TU-100 is an effective treatment option after hepatic resection in patients with liver cancer.

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Abbreviations

TU-100:

Daikenchuto

JFMC:

Japanese Foundation for Multidisciplinary Treatment of Cancer

FBM-T:

The time from extubation until the first postoperative bowel movement

CRP:

C-reactive protein

COX-2:

Cyclooxygenase-2

CGRP:

Calcitonin gene-related peptide

VIP:

Vasoactive intestinal polypeptide

AUC:

Area under curve

SD:

Standard deviation

CRLR:

Calcitonin receptor like receptor

Ramp1:

Receptor activity modifying protein 1

ADM:

Adrenomedullin

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Acknowledgments

This work was jointly supported by the Japanese Foundation for Multidisciplinary Treatment of Cancer.

Conflict of interest

Mitsuo Shimada received the research grant by TSUMURA & CO. (Tokyo, Japan). The other authors declare that they have no conflict of interest.

Author information

Affiliations

  1. Department of Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan

    Mitsuo Shimada & Yuji Morine

  2. Department of Surgery, Osaka University, Osaka, Japan

    Hiroaki Nagano

  3. Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Etsuro Hatano

  4. Department of Surgery, Kimitsu Chuo Hospital, Chiba, Japan

    Takashi Kaiho

  5. Department of General Surgery, Chiba University Graduate School of Medicine, Chiba, Japan

    Masaru Miyazaki

  6. Sapporo Higashi Tokushukai Hospital, Hokkaido, Japan

    Toru Kono

  7. Department of General Surgery, Hokkaido University Graduate School of Medicine, Hokkaido, Japan

    Toshiya Kamiyama

  8. Department of Biostatistics and Epidemiology, School of Medicine, Yokohama City University, Yokohama, Japan

    Satoshi Morita

  9. Japanese Foundation for Multidisciplinary Treatment of Cancer, Tokyo, Japan

    Junichi Sakamoto & Shigetoyo Saji

  10. Kushiro Rosai Hospital, Hokkaido, Japan

    Mitsuo Kusano

  11. Nagasaki Municipal Hospital, Nagasaki, Japan

    Takashi Kanematsu

  12. International University of Health and Welfare, Tokyo, Japan

    Masaki Kitajima

Authors
  1. Mitsuo Shimada
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  2. Yuji Morine
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  3. Hiroaki Nagano
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  4. Etsuro Hatano
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  5. Takashi Kaiho
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  6. Masaru Miyazaki
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  7. Toru Kono
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  8. Toshiya Kamiyama
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  9. Satoshi Morita
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  10. Junichi Sakamoto
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  11. Mitsuo Kusano
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  12. Shigetoyo Saji
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  13. Takashi Kanematsu
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  14. Masaki Kitajima
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Corresponding author

Correspondence to Mitsuo Shimada.

Additional information

For the JFMC40-1001 group.

Appendix

Appendix

The members of this multicenter, phase III trial (JFMC40-1001) group were as follows:

Steering Committee: Mitsuo Kusano, Junichi Sakamoto, Mitsuo Shimada, Toru Kono, Takashi Kaiho, Toshiya Kamiyama, Hiroaki Nagano, Minoru Tanabe, Yuji Morine;

Medical Advisors: Masaki Kitajima, Takashi Kanematsu, Shigetoyo Saji;

Independent Data and Safety Monitoring Committee: Masaru Miyazaki, Kazuhiro Hanasaki;

Statistical Analyst: Satoshi Morita.

Principal Investigators (all in Japan): Hokkaido University Hospita—T. Kamiyama, K. Nakanishi; Supporo Medical University—K. Hirata, T. Mizuguchi; Kushiro Rosai Hospital—K. Ogasawara; Hitachi General Hospital—M. Okumura, K. Ueda; Fukaya Red Cross Hospital—H. Ito; Kameda General Hospital—N. Kano, S. Yamada; Kimitsu Chuo Hospital—T. Kaiho; Toho University Omori Medical Center—H. Kaneko, Y. Otsuka; Tokyo Medical University Hachioji Medical Center—M. Shimazu, Y. Abe; Toyama University Hospital—K. Tsukada, K. Matsui; Fujita Health University—A. Sugioka, T. Tokoro; Fujita Health University School of Medicine Banbuntane Hotokukai Hospital—Z. Morise; Kyoto University Hospital—E. Hatano, K. Taura; Osaka Medical Center for Cancer and Cardiovascular Diseases—T. Yamada, K. Goto; Osaka City University Hospital—S. Kubo, T. Uenishi; Osaka General Medical Center—K. Nishikawa, T. Deguchi; Osaka University—H. Nagano, S. Kobayashi; Osaka Medical College—K. Uchiyama, M. Hayashi; National Hospital Organization Osaka Minami Medical Center—K. Tabuse, Y. Shono; Tokushima University Hospital—M. Shimada, Y. Morine; Kyusyu University Hospital—Y. Maehara, K. Shirabe; Iizuka Hospital—K. Kajiyama, N. Harimoto; Nagasaki University Graduate School of Biomedical Science—S. Eguchi, M. Takatsuki; Kumamoto University Hospital—H. Baba, T. Beppu; Oita University Hospital—S. Kitano, M. Ota; Kagoshima University Hospital—S. Natsugoe, S. Ueno.

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Shimada, M., Morine, Y., Nagano, H. et al. Effect of TU-100, a traditional Japanese medicine, administered after hepatic resection in patients with liver cancer: a multi-center, phase III trial (JFMC40-1001). Int J Clin Oncol 20, 95–104 (2015). https://doi.org/10.1007/s10147-014-0678-2

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  • DOI: https://doi.org/10.1007/s10147-014-0678-2

Keywords

  • Japanese medicine
  • Bowel movement
  • Inflammation
  • C-reactive protein
  • Liver damage