Exploring the Role of Rikkunshito for Chemotherapy‐Induced Anorexia ( <scp>RICH</scp> Trial): Insight From Plasma Metabolomics

ABSTRACT Aim Cisplatin is a key chemotherapeutic drug used for lung cancer therapy; however, it is known to induce gastrointestinal disorders. The aim of the present trial was to determine the efficacy of the Traditional Japanese (Kampo) Medicine rikkunshito (TJ‐43) in preventing cisplatin‐induced anorexia caused by chemotherapy. Patients with lung cancer scheduled to receive cisplatin‐including chemotherapy were deemed eligible. Trial Design This placebo‐controlled, double‐blind, randomized trial was conducted to evaluate the efficacy of TJ‐43 in treating chemotherapy‐induced anorexia and maintaining food intake in lung cancer patients undergoing cisplatin‐based chemotherapy. Methods Patients were randomly allocated to receive either TJ‐43 or placebo in a 1:1 ratio. The primary endpoint was the change in dietary intake. Additionally, plasma metabolomics analysis was performed to explore biomarkers associated with the efficacy of TJ‐43. Results A total of 60 patients were enrolled in the present trial and the patient characteristics of the two groups were similar. Notably, there was no statistically significant difference in the mean dietary intake between the two groups [TJ‐43 treatment group (95% CI): 425.2 g (386.1–464.4); placebo treatment group: 431.9 g (394.1–469.7)]. By contrast, in the metabolomics analysis, acetylglycine, arabinose, isocitric acid and 3‐phosphoglyceric acid levels in the plasma were revealed to be related to the effect of TJ‐43 on food intake and the overall quality of life. Conclusion In conclusion, although no significant impact on food intake was observed, the identification of plasma metabolites associated with TJ‐43 responsiveness suggests its potential use in targeted therapeutic approaches. Trail Registration: This trial was registered in the Japan Registry of Clinical Trials (jRCT) registry as jRCT1080222695