This study aimed to explore the clinical efficacy and underlying mechanisms of Banxia Xiexin Decoction (半夏泻心汤) in treating delayed-onset diarrhea induced by CPT-11 chemotherapy in the patients with advanced colorectal cancer. The primary focus was to evaluate its potential antidiarrheal mechanisms through gut microbiota modulation, providing scientific evidence for integrating traditional Chinese medicine (TCM) with Western medicine in the treatment of chemotherapy-related diarrhea.

A total of 103 patients with advanced colorectal cancer who developed cold-heat mixed type delayedonset diarrhea following CPT-11 chemotherapy were recruited from the Department of Integrated Traditional Chinese and Western Medicine Oncology, Affiliated Hospital of Southeast University School of Medicine (Jiangyin People's Hospital) between July 2022 and June 2024. The patients were randomly assigned to either the experimental group (51 patients, treated with Banxia Xiexin Decoction combined with Montmorillonite Powder) or the control group (52 patients, treated with Montmorillonite Powder alone). Both groups received treatment for 2 weeks, and the use of antibiotics, probiotics or other medications that could affect gut microbiota was prohibited. The primary outcome measures included the severity of diarrhea (assessed using the NCI CTCAE 5.0 grading system), TCM symptom scores, gut microbiota composition (analyzed using 16S rDNA high-throughput sequencing), quality of life [Karnofsky performance status scale (KPS) score and inflammatory cytokine levels [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6)]. Secondary outcomes included clinical efficacy (response rate and total effective rate) and safety of the treatment. Adverse events were recorded and evaluated.

After treatment, the severity of diarrhea (NCI CTCAE grading) and TCM symptom scores in the experimental group were significantly lower than those in the control group (P<0.05). The response rate and total effective rate in the experimental group were 54.9% (28/51) and 94.1% (48/51), respectively, significantly higher than those [26.9% (14/52) and 73.1% (38/52)] in the control group (P<0.05). 16S rDNA sequencing results showed that the gut microbiota diversity in the experimental group was significantly increased (P<0.05), with a higher proportion of Firmicutes and a significant decrease in the proportion of pathogenic bacteria such as Bacteroidetes and Proteobacteria (P<0.05) compared to those in the control group. The serum levels of TNF-α and IL-6 were significantly lower in the experimental group (P<0.05), with a greater reduction compared to those in the control group. KPS scores indicated a significant improvement in the quality of life of the patients in the experimental group (P<0.05). In terms of safety, no serious adverse reactions occurred in either group. A few patients experienced mild nausea or dry mouth, which did not require special treatment.

Banxia Xiexin Decoction significantly improves delayed-onset diarrhea induced by CPT-11 chemotherapy in the patients with advanced colorectal cancer. The potential mechanism may involve the modulation of gut microbiota, reduction in pathogenic bacteria and restoration of gut microbial balance. Furthermore, Banxia Xiexin Decoction enhances patients' quality of life and demonstrates good safety. This study provided new evidence for the clinical application and mechanistic research of traditional Chinese medicine in chemotherapy-related diarrhea.