Application of intestinal fungus pill combined with capecitabine in treatment of advanced colorectal cancer

Abstract

The application discloses application of intestinal mushroom pills combined with capecitabine in treatment of advanced colorectal cancer and comprises the following contents: ① a traditional Chinese medicine prescription: the intestinal mushroom pills are composed of the following components in parts by weight: Gleditsia sinensis 40-50 parts, prepared Aconitum 2-4 parts, Poria cocos 25-35 parts, Evodia rutaecarpa 2-4 parts, Coptis chinensis 15-20 parts, Areca catechu 8-10 parts, Corydalis 8-10 parts, Zingiber officinale 8-10 parts, Rhizoma Pinelliae praeparatum 8-10 parts, Radix et Rhizoma Rhei 8-10 parts, Ramulus Cinnamomi 8-10 parts, Citrus aurantium 10-15 parts, Fructus Aurantii Immaturus 8-10 parts, and Amomum villosum 2-5 parts; ② western medicine: capecitabine tablets; the traditional Chinese medicine intestinal mushroom pills are combined with the capecitabine tablets.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to the application of intestinal fungus pills combined with capecitabine in the treatment of advanced colorectal cancer. Background Technology

[0002] Studies show that approximately one-quarter of patients are initially diagnosed with advanced colorectal cancer, while another quarter progress to advanced colorectal cancer after metastasis following diagnosis. Current treatment options focus on the following: 1. Surgical treatment: For locally advanced or resectable metastatic colorectal cancer, surgical resection is often the preferred treatment. This may include removing the primary tumor and any metastatic lesions, such as liver or lung metastases. In some cases, preoperative chemotherapy or radiotherapy may be necessary to shrink the tumor, thereby improving surgical success rates. 2. Chemotherapy: Chemotherapy is one of the main treatments for advanced colorectal cancer and can be used as first-, second-, or third-line therapy. Commonly used chemotherapy drugs include 5-FU / LV, irinotecan, oxaliplatin, and capecitabine. The choice of chemotherapy regimen depends on the patient's specific circumstances, such as KRAS, NRAS, BRAF gene status, and microsatellite stability (MSI). 3. Radiotherapy: For locally advanced rectal cancer, radiotherapy can be used as an adjuvant therapy to help shrink the tumor and reduce the risk of local recurrence. In some cases, preoperative radiotherapy may be more beneficial. 4. Targeted therapy: Targeting specific molecular targets, such as vascular endothelial growth factor (VEGF) or epidermal growth factor receptor (EGFR), targeted therapy can be used in combination with chemotherapy to improve treatment efficacy. Bevacizumab is a commonly used drug targeting VEGF, while cetuximab targets EGFR.

[0003] However, some patients with advanced colorectal cancer often refuse standard Western medicine treatment due to advanced age, poor physical condition, and concerns about the severe side effects of chemotherapy (such as the potential for long-term chemotherapy to lead to decreased physical function and quality of life). Furthermore, some patients who have already received standard Western medicine treatment are unwilling to endure the pain of chemotherapy again, or their weakened physical condition makes them unable to tolerate standard Western medicine treatment, thus seeking traditional Chinese medicine (TCM) or integrated TCM and Western medicine treatments. TCM has shown good clinical efficacy in the diagnosis and treatment of advanced colorectal cancer, especially in improving patients' quality of life and prolonging their survival.

[0004] Therefore, it is of great significance to develop a traditional Chinese medicine that can be used in conjunction with Western medicine to treat colorectal cancer based on the theory of traditional Chinese medicine. Summary of the Invention

[0005] The purpose of this invention is to provide the application of intestinal fungus pills combined with capecitabine in the treatment of advanced colorectal cancer, and to provide a drug combination therapy scheme of traditional Chinese and Western medicine for the treatment of advanced colorectal cancer. Through the adjuvant effect of traditional Chinese medicine, the side effects of chemotherapy drugs can be reduced, the treatment effect can be improved, and the quality of life of patients can be improved.

[0006] The application of the mushroom pills combined with capecitabine provided by this invention in the treatment of advanced colorectal cancer includes the following:

[0007] 1. Traditional Chinese Medicine Formula: Intestinal Fungus Pill

[0008] Composition by weight: 40-50 parts of Gleditsia sinensis thorns, 2-4 parts of processed Aconitum carmichaelii, 25-35 parts of Poria cocos, 2-4 parts of Evodia rutaecarpa, 15-20 parts of Coptis chinensis, 8-10 parts of Areca catechu, 8-10 parts of Corydalis yanhusuo, 8-10 parts of dried ginger, 8-10 parts of processed Pinellia ternata, 8-10 parts of rhubarb, 8-10 parts of cinnamon twig, 10-15 parts of Citrus reticulata peel, 8-10 parts of Citrus aurantium, and 2-5 parts of agarwood powder.

[0009] Preparation method: Use a decoction machine to decoct the herbs uniformly and make them into Chinese medicinal slices.

[0010] Instructions for use: The patient should take one dose orally each time, once in the morning and once in the evening.

[0011] 2. Western medicine: Capecitabine tablets

[0012] Instructions for use: Use according to the dosage and frequency prescribed by your doctor.

[0013] Instructions for use

[0014] The traditional Chinese medicine intestinal fungus pills were used in combination with capecitabine tablets. The traditional Chinese medicine was used to reduce the side effects of chemotherapy, improve the patient's physical condition, and increase the patient's tolerance to chemotherapy drugs.

[0015] Furthermore, the formula for the Chinese herbal medicine Intestinal Fungus Pill consists of: 45 parts of Gleditsia sinensis thorns, 3 parts of processed Aconitum carmichaelii, 30 parts of Poria cocos, 3 parts of Evodia rutaecarpa, 18 parts of Coptis chinensis, 9 parts of Areca catechu, 9 parts of Corydalis yanhusuo, 9 parts of dried ginger, 9 parts of processed Pinellia ternata, 9 parts of rhubarb, 9 parts of cinnamon twig, 12 parts of Citrus reticulata peel, 9 parts of Citrus aurantium, and 3 parts of agarwood powder.

[0016] Furthermore, Changxunwan is a traditional Chinese medicine decoction, pill, or tablet.

[0017] The medicinal materials used in the traditional Chinese medicine composition of the present invention are as follows:

[0018] Soapberry thorns contain a variety of natural anti-cancer components, which can inhibit the activity of carcinogens in the human body, clear various viruses in the human body, prevent cell carcinogenesis, and increase the body's anti-cancer ability.

[0019] Processed Aconitum carmichaelii: This refers to the processed form of Aconitum carmichaelii. Aconitum carmichaelii is the dried mother root of Aconitum carmichaelii, a plant in the Ranunculaceae family. Processed Aconitum carmichaelii has significant anti-inflammatory activity, reducing the level of PGE in inflammatory exudates and significantly inhibiting symptoms of rheumatoid arthritis such as foot swelling and increased capillary permeability caused by histamine and serotonin.

[0020] Poria cocos: Poria cocos has the effects of promoting diuresis and reducing swelling, eliminating dampness and soothing the stomach, which is beneficial for edema, abdominal distension and other conditions that may occur in patients with colon cancer;

[0021] Evodia rutaecarpa: Evodia rutaecarpa is the nearly mature fruit of Evodia rutaecarpa, Evodia rutaecarpa or Evodia rutaecarpa var. sparsely hairy, with a pungent and bitter taste, and is hot in nature. It is slightly toxic and has the effects of warming the meridians and dispelling cold, soothing the liver and relieving pain. It also has an inhibitory effect on tumors.

[0022] Coptis chinensis has the effects of clearing heat and drying dampness, purging fire and detoxifying, and clearing away heart, stomach and liver fire.

[0023] Areca nut: In traditional Chinese medicine, areca nut is used as a medicine and has the effects of killing insects, eliminating food stagnation, regulating qi, promoting diuresis and urination.

[0024] Corydalis: 1. Promotes blood circulation: The various chemical components in Corydalis, such as alkaloids, can promote blood circulation, improve blood flow, and eliminate blood stasis. 2. Regulates Qi: Corydalis can regulate the flow of Qi, making it smooth and relieving various symptoms caused by Qi stagnation;

[0025] Dried ginger: The main functions and effects of dried ginger include warming the middle and dispelling cold, warming the lungs and resolving phlegm, and restoring yang and unblocking the meridians.

[0026] Pinellia ternata: It dries dampness and resolves phlegm, and is used for cough and asthma with excessive phlegm, dizziness and palpitations due to phlegm retention, vertigo due to wind-phlegm, and headache due to phlegm syncope.

[0027] Rhubarb: It has the functions of purging and eliminating stagnation, clearing heat and purging fire, cooling blood and detoxifying, and removing blood stasis and promoting menstruation;

[0028] Cinnamon twig: A diaphoretic agent. This product has a variety of pharmacological effects, including promoting sweating, antipyretics, analgesia, dilating skin blood vessels, antimicrobial activity, sedation, anti-inflammation, anticonvulsant, increasing coronary blood flow, cardiotonic, diuretic, promoting gastrointestinal motility, and inhibiting tumors.

[0029] Citrus reticulata peel: It has a pungent and bitter taste, is warm in nature, and enters the lung and spleen meridians. It has the effects of regulating qi and resolving phlegm, promoting digestion, and dispelling cold and dampness.

[0030] Fructus Aurantii Immaturus: A qi-regulating herb. Fructus Aurantii Immaturus has various pharmacological effects, including regulating gastrointestinal motility, anti-ulcer, choleretic, blood pressure raising, cardiotonic, analgesic, increasing coronary, cerebral, and renal blood flow, and inhibiting or stimulating the uterus.

[0031] Agarwood: A medicine for regulating qi. Agarwood has a variety of pharmacological effects, including inhibiting gastrointestinal motility, promoting the secretion of digestive juices, promoting bile secretion, relieving asthma, anesthetic, analgesic, antibacterial, blood pressure lowering, and inhibiting the central nervous system.

[0032] This treatment plan is an integrated traditional Chinese and Western medicine approach developed based on actual clinical practice and considering patients' treatment preferences. It combines capecitabine monotherapy with classic traditional Chinese medicine formulas to achieve a balance between patients' quality of life and survival. This treatment plan is a concrete application of the strategy of integrating traditional Chinese and Western medicine in advanced colorectal cancer, providing an alternative for patients with advanced colorectal cancer who cannot tolerate or refuse standard Western medical treatment. 1. Improve survival and quality of life: Traditional Chinese medicine intervention can prolong the survival of patients with advanced colorectal cancer and improve their quality of life. Studies have shown that chemotherapy combined with traditional Chinese medicine treatment can significantly improve patient survival, reduce the toxic side effects of chemotherapy, such as gastrointestinal reactions, bone marrow suppression, and peripheral neuropathy, and increase the completion rate of chemotherapy compared to chemotherapy alone; 2. Reduce chemotherapy side effects: Traditional Chinese medicine can reduce the toxic side effects of chemotherapy, such as gastrointestinal reactions, bone marrow suppression, and peripheral neuropathy, improving patients' tolerance and quality of life; 3. Integrated traditional Chinese and Western medicine treatment: In the treatment of advanced colorectal cancer, integrated traditional Chinese and Western medicine treatment can improve the treatment effect. Traditional Chinese medicine (TCM) treatment can further improve the efficacy of Western medicine standard treatment, while also alleviating patients' clinical symptoms and improving their quality of life. Attached Figure Description

[0033] Figure 1 This represents the progression-free survival rate for patients with advanced colorectal cancer in this embodiment.

[0034] Figure 2 This example shows the patients who benefited and those who did not.

[0035] Figure 3 This example compares progression-free survival in patients with different disease sites.

[0036] Figure 4 This example compares progression-free survival for patients with different tumor burdens.

[0037] Figure 5 This example compares progression-free survival for patients with different genetic states.

[0038] Figure 6 This example compares progression-free survival for patients with different KPS scores.

[0039] Figure 7 This example compares the progression-free survival of patients who took intestinal mushroom pills orally for different durations.

[0040] Figure 8 This example compares the progression-free survival of patients with different TCM syndrome differentiations.

[0041] Figure 9 This example compares the progression-free survival of patients with different TCM pathological factors. Detailed Implementation

[0042] The present invention will now be described in further detail with reference to the accompanying drawings and embodiments:

[0043] Example 1

[0044] 1.1 Target Audience

[0045] Sixty patients with advanced colorectal cancer who visited our hospital were selected and treated with a regimen of intestinal mushroom pills combined with capecitabine. Fifty-two patients were ultimately included in the data analysis, and eight were excluded (six patients discontinued medication on their own, and two patients' families refused visits). Of the 52 patients, 34 were male and 18 were female, aged 39–89 years, with a mean age of 60.9 ± 9.8 years. Twenty-seven patients were over 60 years old, and 25 patients were under 60 years old.

[0046] 1.2 Sample Size Estimation

[0047] This is a single-arm clinical study, and the sample size was calculated using the formula for a population mean:

[0048] N=(Zα / 2+Zβ)^2×σ^2 / δ^2

[0049] Where N is the required sample size, Zα / 2 is the Z-value of the significance level, Zβ is the Z-value of the statistical power, σ is the population standard deviation, and δ is the effect size of interest. Finally, the required sample size was calculated to be no less than 42 cases. With a dropout and loss to follow-up rate set at ≤15%, the final sample size N = 50. To ensure the highest possible confidence level, this study plans to include a total sample size of 60 cases.

[0050] 1.3 Ethical Review

[0051] This clinical study was approved by the Ethics Committee of the Affiliated Three Gorges Hospital of Chongqing University (Ethics Review Approval No.: 2023 Kelun Review No. (184)) and registered with the Chinese Clinical Trial Registry (Registration No.: ChiCTR2300077794).

[0052] 1.4 Diagnostic criteria

[0053] The diagnosis of advanced colorectal cancer is based on the "Guidelines for the Diagnosis and Treatment of Colorectal Cancer of the Chinese Society of Clinical Oncology 2021", and the staging criteria are based on the TNM staging of colon and rectal cancer in the "AJCC Cancer Staging Manual 2017".

[0054] 1.5 Inclusion Criteria

[0055] ① Age ≥ 18 years, gender not limited; ② Pathological stage of advanced colorectal cancer with no chance of radical surgery; ③ Karnofsky Performance Score (KPS) ≥ 60 points; ④ Expected survival ≥ 3 months; ⑤ No severe cardiac, pulmonary, hepatic, or renal dysfunction; ⑥ Non-grade II or higher diarrhea (CTCAE v4.03 classification); ⑦ Measurable lesions meeting RECIST 1.1 criteria; ⑧ Good adherence, able to follow up on efficacy and non-recurrence as required by the protocol; ⑨ Voluntarily join this study and sign an informed consent form.

[0056] 1.6 Exclusion Criteria

[0057] ① Concurrent malignant tumors; ② Concurrent severe heart, liver, and kidney diseases and complications; ③ Multiple factors affecting the absorption of oral medications, such as dysphagia or intestinal obstruction; ④ Any unstable condition that may endanger patient safety and study compliance; ⑤ Subjects whose compliance is poor or who cannot cooperate to complete the study as determined by the investigator; ⑥ Other situations deemed unsuitable for inclusion by the investigator.

[0058] 1.7 Rejection Criteria

[0059] ① Patients who, for whatever reason, are unwilling or unable to continue the clinical study and request to withdraw from the study by their attending physician; ② Study subjects who, although not explicitly requesting withdrawal, have stopped receiving medication and testing, resulting in loss to follow-up; ③ Violation of inclusion or exclusion criteria, or poor subject compliance, failing to complete the full course of medication according to the study protocol; ④ The occurrence of intolerable adverse reactions or other safety events.

[0060] 2 methods

[0061] 2.1 Treatment Plan

[0062] All enrolled patients took the intestinal fungus pills and capecitabine tablets orally daily until disease progression or death from any cause. ① Intestinal fungus pills consist of: 45g of Gleditsia sinensis thorns, 3g of processed Aconitum carmichaelii, 30g of Poria cocos, 3g of Evodia rutaecarpa, 18g of Coptis chinensis, 9g of Areca catechu, 9g of Corydalis yanhusuo, 9g of dried ginger, 9g of processed Pinellia ternata, 9g of Rheum palmatum, 9g of Cinnamomum cassia, 12g of Citrus reticulata peel, 9g of Citrus aurantium, and 3g of Aquilaria sinensis powder, etc. The Chinese herbal medicine pieces used were provided by the National Pharmacy of the Affiliated Three Gorges Hospital of Chongqing University, and were uniformly decocted using a decoction machine. Patients took one dose orally daily, twice a day, morning and evening. ② Capecitabine tablets (Jiangsu Hengrui Medicine Co., Ltd., specification 500mg / tablet, National Drug Approval Number H20133365): 3 tablets twice daily, dosage can be adjusted according to adverse reactions.

[0063] 2.2 Observation Indicators

[0064] 2.2.1 Indicators for judging efficacy

[0065] Progression-free survival (PFS) refers to the time from the start of treatment until disease progression or death from any cause is observed. Based on the median PFS of current Western medical treatments, patients are categorized as benefiting or non-benefiting patients.

[0066] 2.2.2 Key Observation Indicators

[0067] Baseline information for all patients was collected, including the number of lines of treatment, pathological classification, gene mutation status, primary tumor site, tumor burden, KPS score, syndrome differentiation, pathological factors, etc., and the benefits of patients under different baseline characteristics were analyzed.

[0068] 2.2.3 Safety Indicators

[0069] Record and evaluate the blood biochemistry, routine blood tests, and adverse events (WHO criteria) of all patients before, during, and after treatment.

[0070] 2.3 Statistical Methods

[0071] Statistical analysis was performed using SPSS 23.0 and Prism 8.0. Progression-free survival (PFS) data were estimated using the Kaplan-Meier method, and survival curves were plotted. The Log-rank test was used to compare survival rates. Descriptive statistics were used to summarize the patients' clinical characteristics. Measurement data that conformed to a normal distribution were expressed as mean ± standard deviation (x ± s); those that did not were expressed as median. Categorical data were expressed as frequency and percentage. All statistical tests were two-tailed, and p < 0.05 was considered statistically significant.

[0072] 3 Results

[0073] 3.1 Baseline Data Analysis

[0074] A total of 52 patients with advanced colorectal cancer who received the combination of intestinal mushroom pills and capecitabine were included in the statistical analysis. The baseline data of the patients are shown in Table 1.

[0075] Table 1. Baseline characteristics of patients with advanced colorectal cancer (52 cases)

[0076]

[0077] 3.2 Efficacy Analysis

[0078] The median progression-free survival (PFS) of the 52 patients included in the statistical analysis was 7.3 months, with 30.1% of patients having a PFS exceeding 12.0 months. See below for detailed results. Figure 1(n=52). Further analysis revealed that 35 patients benefited from this treatment regimen (red portion in the graph), while 17 patients did not benefit from this treatment regimen (green portion in the graph). See details below. Figure 2 .

[0079] Stratified analysis of lesion location showed that the median progression-free survival (PFS) for patients diagnosed with colon cancer (n=34) and rectal cancer (n=18) was 9.4 months and 4.7 months, respectively, with a statistically significant difference (P<0.05). See details below. Figure 3 .

[0080] Tumor burden stratification analysis showed that the median progression-free survival (PFS) for patients with advanced colorectal cancer with high (n=11), medium (n=18), and low (n=23) tumor burdens were 7.0 months, 4.7 months, and 10.8 months, respectively; the differences were statistically significant (P<0.05). For detailed results, please refer to [link to relevant documentation]. Figure 4 .

[0081] Stratified analysis of tumor gene status revealed that one patient's gene status was unknown (not included in the analysis). The median progression-free survival (PFS) for patients with advanced colorectal cancer of RSA / RAF wild-type (n=22) and mutant (n=29) was 7.9 months and 6.9 months, respectively; the difference was not statistically significant (P>0.05). For detailed results, please refer to [link to relevant documentation]. Figure 5 .

[0082] Stratified analysis of patients with different KPS scores showed that the median progression-free survival (PFS) was 7.9 months for patients with advanced colorectal cancer and 6.5 months for those with KPS scores ≥80 (n=37) and ≤70 (n=15), respectively; the difference was statistically significant (P<0.05). See details below. Figure 6 .

[0083] Stratified analysis of patients treated with intestinal fungus pills for different durations showed that the median progression-free survival (PFS) was 8.0 months, 5.2 months, and 4.2 months for patients treated for ≥6 months (n=25), 3–6 months (n=15), and ≤3 months (n=12), respectively; the differences were statistically significant (P<0.05). See details below. Figure 7 .

[0084] Stratified analysis of patients based on TCM syndrome differentiation showed that the median progression-free survival (PFS) for patients with TCM visceral syndrome differentiation including spleen (n=42), kidney (n=35), liver (n=20), and lung (n=7) was 8.3 months, 6.7 months, 7.3 months, and 5.6 months, respectively; the differences were statistically significant (P<0.05). See below for details. Figure 8 .

[0085] Stratified analysis of patients with different TCM pathological factors showed that the median progression-free survival (PFS) for patients with TCM pathological factors including phlegm (n=46), dampness (n=8), and blood stasis (n=42) was 7.0 months, 7.3 months, and 6.5 months, respectively; the differences were not statistically significant (P>0.05). See details below. Figure 9 .

[0086] 3.2 Security Analysis

[0087] Of the 52 patients included in the statistical analysis, none died from treatment-related causes. Common adverse reactions were anemia (n=23), leukopenia (n=18), decreased appetite (n=22), fatigue (n=17), and hand-foot syndrome (n=9), with incidence rates of 44.2%, 34.6%, 42.3%, 32.7%, and 17.3%, respectively. The incidence of grade 3 or higher adverse events was 13.5% (7 cases), including 5 hematological adverse events and 2 non-hematological adverse events. Detailed results are shown in Table 2.

[0088] Table 2. Occurrence of common adverse events (52 cases)

[0089]

[0090] This treatment plan is an integrated traditional Chinese and Western medicine approach developed based on actual clinical practice and the patient's treatment preferences. It combines capecitabine monotherapy with classic traditional Chinese medicine formulas to achieve a balance between the patient's quality of life and survival. This treatment plan represents a specific application of the strategy of integrating and emphasizing both traditional Chinese and Western medicine in advanced colorectal cancer, providing an alternative for patients with advanced colorectal cancer who cannot tolerate or refuse standard Western medical treatment.

[0091] This clinical study included 60 patients with advanced colorectal cancer who refused or could not tolerate standard Western medicine treatment. Eight patients dropped out due to self-discontinuation of medication or loss to follow-up, with the dropout rate within the quality control range for clinical studies. The results showed that the median progression-free survival (PFS) in the 52 patients with advanced colorectal cancer included in the data analysis was 7.3 months, with 30.1% of patients having a PFS exceeding 12.0 months; this was more effective than the OPTIMOX study (median PFS of 6.4 months). The combination of intestinal fungus pills and capecitabine resulted in no death-related adverse events. Common adverse reactions included leukopenia, anemia, decreased appetite, fatigue, and hand-foot syndrome, most of which were manageable grade 1-2 adverse reactions. Further analysis of the baseline characteristics of benefiting patients revealed that patients with low tumor burden, colonic lesions, KPS scores ≥80, long-term oral administration of traditional Chinese medicine, and TCM syndrome differentiation indicating spleen or liver involvement had better progression-free survival, suggesting that these patients are more suitable for the treatment regimen of Changxunwan combined with capecitabine. However, there was no significant difference in progression-free survival among patients with different TCM pathological factors and different gene states, indicating that these two baseline characteristics do not affect whether patients benefit from the Changxunwan combined with capecitabine regimen. Therefore, in clinical practice, it is strongly recommended that patients with advanced colorectal cancer who have low tumor burden, colonic lesions, KPS scores ≥80, or TCM syndrome differentiation indicating spleen or liver involvement adopt the integrated TCM and Western medicine treatment regimen of Changxunwan combined with capecitabine, as they can significantly benefit from the treatment.

[0092] Capecitabine is a commonly used oral chemotherapy drug for the clinical treatment of advanced colorectal cancer. Common adverse reactions include hematologic toxicity (such as decreased white blood cell count, decreased hemoglobin, and decreased platelet count), and non-hematologic toxicity includes gastrointestinal reactions, abnormal liver and kidney function, and hand-foot reactions. Intestinal fungus pills have the effects of strengthening the body's resistance, eliminating pathogenic factors, warming the yang and promoting bowel movement, and dispersing nodules and reducing swelling, with good clinical efficacy. Combining intestinal fungus pills, which treat intestinal accumulation, with capecitabine for advanced colorectal cancer patients who cannot tolerate or refuse standard Western medicine treatment has a good theoretical basis and clinical feasibility, and is one of the characteristic forms and methods of integrated traditional Chinese and Western medicine treatment for advanced colorectal cancer. The results of this clinical study show that patients with advanced colorectal cancer who have low tumor burden, are located in the colon, have a KPS score ≥80, and whose TCM diagnosis includes spleen or liver, benefit more significantly. However, patients with advanced colorectal cancer who have different TCM pathological factors or different gene states do not seem to benefit significantly. In addition, this embodiment also incorporates the latest research progress in colorectal cancer, taking tumor burden, gene type, and location of onset as factors, which supplements and enriches the scientific connotation of the clinical application of Changxun Pill in advanced colorectal cancer and has important clinical value.

[0093] In summary, this clinical study compared the clinical efficacy of patients with advanced colorectal cancer treated with a combination of capecitabine and enoki mushroom pills with that of the OPTIMOX study. The conclusion is that patients treated with capecitabine combined with enoki mushroom pills experience improved clinical benefit. Further analysis revealed the baseline characteristics of these benefiting patients, providing a preliminary summary of the optimal patients for this treatment regimen.

[0094] This specific embodiment is merely an explanation of the present invention and is not intended to limit the invention. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they are within the scope of the claims of the present invention.

Claims

1. The application of intestinal mushroom pills combined with capecitabine in the treatment of advanced colorectal cancer, characterized in that, Includes the following: ① Traditional Chinese medicine formula: Intestinal Fungus Pill Composition by weight: 40-50 parts of Gleditsia sinensis thorns, 2-4 parts of processed Aconitum carmichaelii, 25-35 parts of Poria cocos, 2-4 parts of Evodia rutaecarpa, 15-20 parts of Coptis chinensis, 8-10 parts of Areca catechu, 8-10 parts of Corydalis yanhusuo, 8-10 parts of dried ginger, 8-10 parts of processed Pinellia ternata, 8-10 parts of rhubarb, 8-10 parts of cinnamon twig, 10-15 parts of Citrus reticulata peel, 8-10 parts of Citrus aurantium, and 2-5 parts of agarwood powder; Preparation method: decocted using a decoction machine to produce prepared Chinese herbal medicine slices; Dosage: One dose is taken orally each time, twice a day, morning and evening. ②Western medicine: Capecitabine tablets; Dosage and administration: Use according to the doctor's prescribed dosage and frequency; Instructions for use: Use the traditional Chinese medicine intestinal fungus pills in combination with capecitabine tablets.

2. The application of the intestinal mushroom pills combined with capecitabine according to claim 1 in the treatment of advanced colorectal cancer, characterized in that, The traditional Chinese medicine formula consists of: 45 parts of Gleditsia sinensis thorns, 3 parts of processed Aconitum carmichaelii, 30 parts of Poria cocos, 3 parts of Evodia rutaecarpa, 18 parts of Coptis chinensis, 9 parts of Areca catechu, 9 parts of Corydalis yanhusuo, 9 parts of dried ginger, 9 parts of processed Pinellia ternata, 9 parts of rhubarb, 9 parts of cinnamon twig, 12 parts of Citrus reticulata peel, 9 parts of Citrus aurantium, and 3 parts of agarwood powder.

3. The application of the intestinal mushroom pills combined with capecitabine according to claim 1 in the treatment of advanced colorectal cancer, characterized in that, Intestinal fungus pills are a traditional Chinese medicine preparation, pill, or tablet.

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