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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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients 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\u2009&gt;\u20090.5\u00a0mg\/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 &amp; Co., Tokyo, Japan) at 7.5\u00a0g\/day, divided into three doses (2.5\u00a0g per dose), before, or between meals for 12\u00a0weeks. The primary endpoint is the difference in anti-inflammatory effect between groups, assessed by the change in CRP from baseline to 12\u00a0weeks. 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This trial will evaluate whether TJ-41 can attenuate systemic inflammation related to host\u2013tumor interactions in patients with unresectable or metastatic CRC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>This study was registered in the Japan Registry of Clinical Trials (jRCT) on June 26, 2024 (jRCTs041240051).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00384-026-05197-5","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T17:45:41Z","timestamp":1785260741000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effectiveness of hochuekkito for colorectal cancer management: protocol for the multicenter randomized controlled AMATERAS study"],"prefix":"10.1007","volume":"41","author":[{"given":"Yoshinaga","family":"Okugawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahito","family":"Kitajima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadanobu","family":"Shimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Imaoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikio","family":"Kawamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"Kawamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Mizukoshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Fujikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Iwata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susumu","family":"Saigusa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiki","family":"Ojima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiko","family":"Mohri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Toiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"issue":"3","key":"5197_CR1","first-page":"229","volume":"74","author":"F Bray","year":"2022","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A (2022) Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 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If deemed eligible, informed consent will be obtained from the patients by the attending physicians at the participating institutes. The study will be conducted in accordance with the World Medical Association Declaration of Helsinki of 1996. The study results will be published in a peer-reviewed journal and be presented at national and international conferences.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Tsumura & Co. had no role in the study design or data collection and analysis of the clinical research. YO and YT received a consulting fee from Tsumura & Co. for conference attendance as an ad hoc advisor regarding the basic research. YO received a speaking honoraria from Tsumura & Co. The other authors have no conflicts of interest to declare.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"168"}}