{ "abstract": "Background\n\nSystemic inflammation, a hallmark of cancer, is recognized as a key mechanism underlying malnutrition, sarcopenia, and cancer cachexia. Hochuekkito (TJ-41) is a traditional Japanese Kampo formula composed of ten medicinal plants, and several studies have suggested its anti-inflammatory effects in various diseases. Our recent retrospective study, supported by in vitro experiments, was the first to demonstrate an anti-inflammatory effect of TJ-41 in patients with unresectable or metastatic gastrointestinal cancer, including colorectal cancer (CRC). However, no prospective randomized multicenter clinical trial has evaluated TJ-41 in the palliative setting of malignancies, including CRC.Methods\n\nPatients with unresectable or metastatic CRC who have received at least two prior systemic regimens or are intolerant to standard therapy, and who show an elevated C-reactive protein (CRP) level > 0.5 mg/dL on two consecutive occasions within two months before enrollment, will be eligible. After providing written informed consent, patients will be randomly assigned to the treatment group (standard treatment plus TJ-41) or control group (standard treatment alone). Patients in the treatment group will receive oral TJ-41 (Tsumura & Co., Tokyo, Japan) at 7.5 g/day, divided into three doses (2.5 g per dose), before, or between meals for 12 weeks. The primary endpoint is the difference in anti-inflammatory effect between groups, assessed by the change in CRP from baseline to 12 weeks. Secondary endpoints include the effects of TJ-41 on other inflammatory and nutritional parameters; patient-reported symptoms and quality of life (QOL) using QOL-ACD and EORTC QLQ-C30; cytokine-based anti-inflammatory and anticachectic effects using serial blood specimens; interactions with other appetite-stimulating agents or nutritional products; and effects on antitumor efficacy and adverse events (AEs). Each group will include 44 patients, with recruitment planned from July 1, 2024, to December 31, 2026.Discussion\n\nThis trial will evaluate whether TJ-41 can attenuate systemic inflammation related to host-tumor interactions in patients with unresectable or metastatic CRC.Trial registration\n\nThis study was registered in the Japan Registry of Clinical Trials (jRCT) on June 26, 2024 (jRCTs041240051).", "abstract_shown": true, "affiliations": [ "Department of Genomic Medicine, Mie University Hospital, Tsu City, Mie, Japan. yosinaga@med.mie-u.ac.jp.", "Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu City, Mie, Japan. yosinaga@med.mie-u.ac.jp.", "Department of Genomic Medicine, Mie University Hospital, Tsu City, Mie, Japan.", "Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu City, Mie, Japan.", "Department of Gastrointestinal and General Surgery, Mie Prefectural General Medical Center, Yokkaichi City, Mie, Japan.", "Department of Surgery, Kuwana City Medical Center, Kuwana City, Mie, Japan.", "Department of Surgery, IGA City General Hospital, Iga City, Mie, Japan.", "Oncology Center, Aichi Medical University School of Medicine and Hospital, Nagakute City, Aichi, Japan.", "Department of Surgery, Doshinkai Tohyama Hospital, Tsu City, Mie, Japan.", "Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu City, Mie, Japan. ytoi0725@med.mie-u.ac.jp." ], "article_type": "research article", "arxiv": null, "author_total": 15, "authors": [ { "affs": [ 0, 1 ], "name": "Yoshinaga Okugawa" }, { "affs": [ 2, 3 ], "name": "Takahito Kitajima" }, { "affs": [ 3 ], "name": "Tadanobu Shimura" }, { "affs": [ 3 ], "name": "Hiroki Imaoka" }, { "affs": [ 3 ], "name": "Mikio Kawamura" }, { "affs": [ 4 ], "name": "Akira Yamamoto" }, { "affs": [ 5 ], "name": "Aya Kawamoto" }, { "affs": [ 5 ], "name": "Kosuke Mizukoshi" }, { "affs": [ 6 ], "name": "Hiroyuki Fujikawa" }, { "affs": [ 7 ], "name": "Takashi Iwata" }, { "affs": [ 6 ], "name": "Susumu Saigusa" }, { "affs": [ 4 ], "name": "Eiki Ojima" }, { "affs": [ 8 ], "name": "Yasuhiro Inoue" }, { "affs": [ 4 ], "name": "Yasuhiko Mohri" }, { "affs": [ 9 ], "name": "Yuji Toiyama" } ], "bibtex": "https://research.draconitic.com/paper/bkqaq2vvbaka7.bib", "cited_by": 0, "doi": "10.1007/s00384-026-05197-5", "fulltext_url": "https://europepmc.org/articles/PMC13694435", "id": "bkqaq2vvbaka7", "issns": [ "0179-1958", "1432-1262" ], "landing_url": "https://europepmc.org/article/MED/42909621", "language": "eng", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2707|Medical Research and Treatments" ] ], "openalex": "W7171511497", "pdf_url": "https://europepmc.org/articles/PMC13694435?pdf=render", "pmcid": "PMC13694435", "pmid": "42909621", "published": "2026-07-28", "publisher": null, "ris": "https://research.draconitic.com/paper/bkqaq2vvbaka7.ris", "sources": [ { "first_seen": "2026-10-30T12:20:14Z", "native_id": "MED:42909621", "source": "europepmc", "url": "https://europepmc.org/article/MED/42909621" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2707|Medical Research and Treatments", "subfield": "general" } ], "title": "Effectiveness of hochuekkito for colorectal cancer management: protocol for the multicenter randomized controlled AMATERAS study.", "title_text": "Effectiveness of hochuekkito for colorectal cancer management: protocol for the multicenter randomized controlled AMATERAS study.", "type": "peer-reviewed", "updated_at": "2026-10-30T12:20:14Z", "url": "https://research.draconitic.com/paper/bkqaq2vvbaka7", "venue": "International journal of colorectal disease", "versions": [] }