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.
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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