Dynamic Treatment Strategy of Chinese Medicine for Metastatic Colorectal Cancer Based on Machine Learning Algorithm.

OBJECTIVE: To establish the dynamic treatment strategy of Chinese medicine (CM) for metastatic colorectal cancer (mCRC) by machine learning algorithm, in order to provide a reference for the selection of CM treatment strategies for mCRC. METHODS: From the outpatient cases of mCRC in the Department of Oncology at Xiyuan Hospital, China Academy of Chinese Medical Sciences, 197 cases that met the inclusion criteria were screened. According to different CM intervention strategies, the patients were divided into 3 groups: CM treatment alone, equal emphasis on Chinese and Western medicine treatment (CM combined with local treatment of tumors, oral chemotherapy, or targeted drugs), and CM assisted Western medicine treatment (CM combined with intravenous regimen of Western medicine). The survival time of patients undergoing CM intervention was taken as the final evaluation index. Factors affecting the choice of CM intervention scheme were screened as decision variables. The dynamic CM intervention and treatment strategy for mCRC was explored based on the cost-sensitive classification learning algorithm for survival (CSCLSurv). Patients' survival was estimated using the Kaplan-Meier method, and the survival time of patients who received the model-recommended treatment plan were compared with those who received actual treatment plan. RESULTS: Using the survival time of patients undergoing CM intervention as the evaluation index, a dynamic CM intervention therapy strategy for mCRC was established based on CSCLSurv. Different CM intervention strategies for mCRC can be selected according to dynamic decision variables, such as gender, age, Eastern Cooperative Oncology Group score, tumor site, metastatic site, genotyping, and the stage of Western medicine treatment at the patient's first visit. The median survival time of patients who received the model-recommended treatment plan was 35 months, while those who receive the actual treatment plan was 26.0 months (P=0.06). CONCLUSIONS: The dynamic treatment strategy of CM, based on CSCLSurv for mCRC, plays a certain role in providing clinical hints in CM. It can be further improved in future prospective studies with larger sample sizes.

Efficacy of Quxie Capsule in Metastatic Colorectal Cancer: Long-Term Survival Update of A Double-Blind, Randomized, Placebo Controlled Trial.

OBJECTIVE: To verify the efficacy of Quxie Capsule in patients with metastatic colorectal cancer (mCRC). METHODS: It was a block randomized, double-blind, placebo-controlled trial. Sixty patients with mCRC were randomized into 2 groups at a 1:1 ratio. The patients in the treatment group received conventional therapy including chemotherapy, radiotherapy, targeted therapy and supportive care, and Chinese herbal medicine combined with Quxie Capsule (each capsule of 0.4 g was orally administered at 50 mg/kg, twice daily, day 1-20, in a 30-day course) for 3 months. The patients in the control group received conventional therapy and Chinese herbal medicine combined with placebo for 3 months. Main outcome measures were overall survival (OS) and progression-free survival (PFS). Subgroup analysis was performed according to therapy lines, right or left-sided colon, targeted therapy and RAS gene status to determine the differences in PFS and OS between the two groups. Patients were followed up every 3 months until December 31st, 2018. RESULTS: Median follow-up time was 19.4 months. The median OS was 23.9 months in the treatment group [95% confidence interval (CI) 15.9-28.5] vs. 14.3 months in the control group (95% CI 11.3-21.4, P<;0.05). Hazard ratio (95% CI) was 0.55 (0.31-0.95, P=0.040). There were no significant differences between the two groups in PFS (P>0.05). In the subgroups of ⩾second-line therapy, non-targeted therapy, RAS gene wild type and left-sided colon, the treatment group showed a significant survival benefit compared with the control group (P<;0.05 or P<;0.01), respectively. CONCLUSION: Quxie Capsule can reduce the risk of death and prolong the OS of patients with mCRC. (Registration No. ChiCTR-IOR-16009733).

Effect of Jianpi Bushen Sequential Formula on Adjuvant Chemotherapy of Colon Cancer: Study Protocol for a Randomized Controlled Trial.

BACKGROUND: The side effects of chemotherapy-induced nausea and vomiting (CINV) and myelosuppression reduce the cancer patients' adherence to chemotherapy. Many Chinese patients choose Chinese medicine (CM) during chemotherapy to reduce side effects; however, the evidence is lacking. The efficacy of a CM herbal treatment protocol, Jianpi Bushen Sequential Formula (, JBSF) will be evaluated on chemotherapy completion rate among patients with colon cancer. METHODS: A multi-center double-blind randomized controlled trial (RCT) will be conducted on 400 patients with colon cancer who will receive 8 cycles of adjuvant chemotherapy with oxaliplatin and capecitabine (CAPEOX). Patients will be randomized 1:1 to receive the JBSF or placebo formula. The primary outcome is the overall chemotherapy completion rate. The secondary outcomes include individual chemotherapy completion rate, 4-cycle completion rate of chemotherapy, time to treatment failure, relative dose intensity and treatment toxicity. Follow-up visits will be scheduled before every and after last chemotherapy. DISCUSSION: This study will provide evidence on whether JBSF can improve the chemotherapy completion rate and reduce side effects among patients with colon cancer. (Trial registration: ClinicalTrials.gov, No. NCT03716518).

Effectiveness of Herbal Medicine for Leukopenia/Neutropenia Induced by Chemotherapy in Adults with Colorectal Cancer: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the effectiveness of Chinese Herbal Medicine (CHM) on leukopenia/neutropenia induced by chemotherapy in adults with colorectal cancer (CRC). METHODS: Eight electronic databases were searched from their inception to June 2020. Randomized controlled trials with clarified sequence generation were qualified. Two reviewers independently conducted the screening and data extraction. Methodological quality was assessed using the Risk of Bias tool. RevMan 5.4 was applied to the meta-analysis. RESULTS: Twenty-seven studies involving 1867 participants were qualified, of which 26 were included in the quantitative synthesis. Meta-analysis showed that CHM significantly reduced the incidence of leukopenia induced by chemotherapy (RR = 0.69; 95% CI 0.59-0.82), as well as the grade 3/4 leukopenia (RR = 0.71; 95% CI 0.55-0.90). Meanwhile,CHM decreased the occurrence of neutropenia (RR = 0.52, 95% CI 0.35-0.77), especially for the grades 3/4 neutropenia (RR = 0.42, 95% CI 0.27-0.64). Twenty-six of the included studies focused on the adverse events related to CHM. CONCLUSION: CHM may relieve neutropenia/leukopenia induced by chemotherapy in adults with colorectal cancer.

Exploring the Safety, Effectiveness, and Cost-Effectiveness of a Chinese Patent Medicine (Fufang E'jiao Syrup) for Alleviating Cancer-Related Fatigue: A Protocol for a Randomized, Double-Blinded, Placebo-Controlled, Multicenter Trial.

OBJECTIVE: To provide higher level evidence on the benefits of a Chinese patent medicine (CPM) (Fufang E'jiao Syrup, FFEJS) for alleviating cancer-related fatigue (CRF), this article describes a protocol for a randomized controlled trial. METHODS/DESIGN: We designed a double-blind, placebo-controlled stratified permuted block randomization clinical trial on CRF among 3 types of cancer in China. Participants will be equally allocated to FFEJS group or placebo group according to the randomization sequence and the hospitals they were enrolled at. Each patient will receive 20 ml of either the study formula FFEJS or a placebo formula, 3 times a day for 6 weeks. The follow-up period will be another 4 weeks for safety evaluation. The primary outcome is the difference in improvement of fatigue as measured with the Revised Piper Fatigue Scale-Chinese Version (RPFS-CV). Secondary outcomes include change in fatigue (measured by routine blood panel and hormones in peripheral blood) and QoL (measured by Edmonton symptom assessment scale and Functional Assessment of Cancer Therapy). Patient safety will be measured by liver, renal or cardiac damage, and the risk of FFEJS having a tumor promotion and progression effect will be monitored throughout this study. Cost-effectiveness will also be evaluated mainly by incremental cost per each quality-adjusted life year gained. DISCUSSION: This article describes the study design of a CPM for CRF in patients with advanced cancer through exploring the effectiveness, safety, and cost-effectiveness of FFEJS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04147312. Registered on 1 Sep 2019.

[Effects of zhengqing fengtongning tablet and methotrexate on the serum OPG/RANKL and IL-17 of collagen-induced arthritis rats].

OBJECTIVE: To study the effects of Zhengqing Fengtongning Tablet (ZFT) and methotrexate (MTX) on the expression of osteoprotegerin (OPG), receptor activator of nuclear factor-kappaB ligand (RANKL), and interleukin 17 (IL-17) in collagen-induced arthritis (CIA) rats, thus addressing their bone protection. METHODS: The CIA rat model was established by intradermally injecting type II collagen emulsion from the rats' back and tail. Totally 28 successfully modeled rats [with the arthritis index (AI) more than 2] were randomly divided into the model group, the Chinese medicine (CM) treatment group, the MTX group, and the ZFT + MTX treatment group, 7 rats in each group. Another 7 rats were recruited as the normal control group. Rats were administered from the 7th day of modeling. Rats in the MTX group were treated with MTX at 3.8 mg/kg once a week. Those in the CM group were treated with ZFT at the daily dose of 130 mg/kg, once a day. Those in the ZFT + MTX treatment group were treated with both MTX (at 3.8 mg/kg once a week) and ZFT (at the daily dose of 130 mg/kg, once a day). Those in the model group and the normal control group were administered with normal saline of the equal volume by gastrogavage. All the intervention lasted for 26 days. The destruction of joints in the four limbs were observed using X-ray. The AI was recorded. The expression levels of serum OPG, RANKL, and IL-17 were detected at the end of the experiment. RESULTS: During the whole process, all rats except those in the model group were in a good condition. On the 21st day of modeling the AI of all rats reached the peak, but it decreased after treatment. Compared with the model group, the AI decreased in the CM treatment group, the MTX group, and the ZFT + MTX treatment group with statistical difference (P < 0.05). Compared with the model group, the OPG increased and RANKL decreased in the MTX group; the OPG and OPG/RANKL increased in the CM treatment group; the OPG, RANKL, and OPG/RANKL increased, and IL-17 decreased in the ZFT + MTX treatment group, all showing statistical difference (P < 0.05). Compared with the MTX and the ZFT + MTX treatment group, OPG/RANKL increased and IL-17 decreased in the ZFT + MTX treatment group (both P < 0.05). CONCLUSION: ZFT + MTX could synergistically elevate peripheral OPG/RANKL and down-regulate IL-17 in CIA model rats.