Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2023

Open Access 01-12-2023 | Colon Cancer | Study Protocol

Efficacy and safety of Xian-Lian-Jie-Du optimization decoction as an adjuvant treatment for prevention of recurrence in patients with stage IIIB/IIIC colon cancer: study protocol for a multicentre, randomized controlled trial

Authors: Xuechen Geng, Ziqiang Wang, Li Feng, Yanhong Gu, Renjie Wang, Qinghua Yao, Yangxian Xu, Jianyu Wu, Zhiwei Jiang, Kai Chen, Wenwei Hu, Dongxin Tang, Jiege Huo, Ling Li, Qianqian Bu, Shuoqi Zhao, Bei Zhang, Haibo Cheng

Published in: BMC Complementary Medicine and Therapies | Issue 1/2023

Login to get access

Abstract

Introduction

Colon cancer remains one of the most prevalent cancers worldwide. Unfortunately, there are no recognized and effective therapeutic strategies to prevent tumor recurrence after radical resection and chemotherapy, and the disease-free survival (DFS) in patients with stage IIIB or IIIC disease remains unsatisfactory. Xian-Lian-Jie-Du optimization decoction (XLJDOD) is a Chinese herbal medicine (CHM) empirical prescription, which has been validated experimentally and clinically that could inhibit the progression of colorectal cancer and ameliorate the symptoms. The purpose of this study is to evaluate the efficacy and safety of XLJDOD in prevention of recurrence of colon cancer.

Methods

This study is a multi-center, double-blind, randomized, placebo-controlled trial conducted at 13 hospitals of China. Following the completion of surgery and adjuvant 5- fluorouracil-based chemotherapy, a total of 730 subjects with stage IIIB or IIIC colon cancer will be randomized in a 1:1 ratio to an intervention group (n = 365; XLJDOD compound granule) and a control group (n = 365; Placebo). Patients will receive 6-month treatments and be followed up with 3 monthly assessments for 2 years. The primary outcome is 2-year DFS rate and the secondary outcomes are 1, 2-year relapse rate (RR), overall survival (OS) and quality of life (QoL). Safety outcomes such as adverse events will be also assessed. A small number of subgroup analysis will be carried out to explore the heterogeneity of effects of XLJDOD.

Discussion

The outcomes from this randomized controlled trial will provide objective evidences to evaluate XLJDOD’s role as an adjuvant treatment in colon cancer.

Trial registration

www.​ClinicalTrials.​gov, identifier: NCT05709249. Registered on 31 Jan 2023.
Appendix
Available only for authorised users
Literature
1.
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.PubMedCrossRef
2.
Sargent D, Sobrero A, Grothey A, O’Connell MJ, Buyse M, Andre T, et al. Evidence for cure by adjuvant therapy in colon cancer: observations based on individual patient data from 20,898 patients on 18 randomized trials. J Clin Oncol. 2009;27(6):872–7.PubMedPubMedCentralCrossRef
3.
Boland GM, Chang GJ, Haynes AB, Chiang YJ, Chagpar R, Xing Y, et al. Association between adherence to National Comprehensive Cancer Network treatment guidelines and improved survival in patients with colon cancer. Cancer. 2013;119(8):1593–601.PubMedCrossRef
4.
Feng RM, Zong YN, Cao SM, Xu RH. Current cancer situation in China: good or bad news from the 2018 Global Cancer Statistics? Cancer Commun (Lond). 2019;39(1):22.PubMedCrossRef
5.
Fortea-Sanchis C, Forcadell-Comes E, Martinez-Ramos D, Escrig-Sos J. Modelling the probability of erroneous negative lymph node staging in patients with colon cancer. Cancer Commun (Lond). 2019;39(1):31.PubMedCrossRef
6.
Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin. 2017;67(2):93–9.PubMedCrossRef
7.
Grothey A, Sobrero AF, Shields AF, Yoshino T, Paul J, Taieb J, et al. Duration of adjuvant chemotherapy for stage iii colon cancer. N Engl J Med. 2018;378(13):1177–88.PubMedPubMedCentralCrossRef
8.
Schmoll HJ, Tabernero J, Maroun J, de Braud F, Price T, Van Cutsem E, et al. Capecitabine plus oxaliplatin compared with fluorouracil/folinic acid as adjuvant therapy for stage iii colon cancer: final results of the NO16968 randomized controlled phase iii trial. J Clin Oncol. 2015;33(32):3733–40.PubMedCrossRef
9.
Labianca R, Beretta GD, Kildani B, Milesi L, Merlin F, Mosconi S, et al. Colon cancer. Crit Rev Oncol Hematol. 2010;74(2):106–33.PubMedCrossRef
10.
Shah MA, Renfro LA, Allegra CJ, Andre T, de Gramont A, Schmoll HJ, et al. Impact of patient factors on recurrence risk and time dependency of oxaliplatin benefit in patients with colon cancer: analysis from modern-era adjuvant studies in the adjuvant colon cancer end points (ACCENT) database. J Clin Oncol. 2016;34(8):843–53.PubMedPubMedCentralCrossRef
11.
Kusumoto T, Ishiguro M, Nakatani E, Yoshida M, Inoue T, Nakamoto Y, et al. Updated 5-year survival and exploratory T x N subset analyses of ACTS-CC trial: a randomised controlled trial of S-1 versus tegafur-uracil/leucovorin as adjuvant chemotherapy for stage III colon cancer. ESMO Open. 2018;3(6): e000428.PubMedPubMedCentralCrossRef
12.
Smith TG, Troeschel AN, Castro KM, Arora NK, Stein K, Lipscomb J, et al. Perceptions of patients with breast and colon cancer of the management of cancer-related pain, fatigue, and emotional distress in community oncology. J Clin Oncol. 2019;37(19):1666–76.PubMedPubMedCentralCrossRef
13.
Chen Q, Shu C, Laurence AD, Chen Y, Peng BG, Zhen ZJ, et al. Effect of Huaier granule on recurrence after curative resection of HCC: a multicentre, randomised clinical trial. Gut. 2018;67(11):2006–16.PubMedCrossRef
14.
Zhang S, Chen W, Wang Y, Wu J, Xu L, Yu Y, et al. Chinese herbal prescription Fu-Zheng-Qu-Xie prevents recurrence and metastasis of postoperative early-stage lung adenocarcinoma: a prospective cohort study followed with potential mechanism exploration. Oxid Med Cell Longev. 2021;2021:6673828.PubMedPubMedCentral
15.
Chen YX, Gao QY, Zou TH, Wang BM, Liu SD, Sheng JQ, et al. Berberine versus placebo for the prevention of recurrence of colorectal adenoma: a multicentre, double-blinded, randomised controlled study. Lancet Gastroenterol Hepatol. 2020;5(3):267–75.PubMedCrossRef
16.
Xu Y, Mao JJ, Sun L, Yang L, Li J, Hao Y, et al. Association between use of traditional Chinese medicine herbal therapy and survival outcomes in patients with stage ii and iii colorectal cancer: a multicenter prospective cohort study. J Natl Cancer Inst Monogr. 2017;2017(52):lgx015.PubMedPubMedCentralCrossRef
17.
Yang Y, Ge J, Wu Y, Xu Y, Liang B, Luo L, et al. Cohort study on the effect of a combined treatment of traditional Chinese medicine and Western medicine on the relapse and metastasis of 222 patients with stage II and III colorectal cancer after radical operation. Chin J Integr Med. 2008;14(4):251–6.PubMedCrossRef
18.
Tang M, Zhang W, Qin W, Zou C, Yan Y, He B, et al. Association between oral Chinese herbal medicine and recurrence and metastasis in patients with stages ii and iii colorectal cancer: a cohort study in China. Evidence-based complementary and alternative medicine : eCAM. 2022;2022:8529395.PubMedCrossRef
19.
Shi Q, Liu S, Li W, Zong S, Han S, Yang W, et al. Exploring the medication duration based on the effect of traditional Chinese medicine on postoperative stage I-III colorectal patients: a retrospective cohort study. Oncotarget. 2017;8(8):13488–95.PubMedPubMedCentralCrossRef
20.
Jia R, Liu N, Cai G, Zhang Y, Xiao H, Zhou L, et al. Effect of PRM1201 combined with adjuvant chemotherapy on preventing recurrence and metastasis of stage iii colon cancer: a randomized, double-blind. Placebo-Controlled Clinical Trial Front Oncol. 2021;11: 618793.PubMed
21.
Cheng HB, Shen WX. [Relevance of cancer toxin pathogenesis theory with transformation of inflammation to carcinoma]. Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine. 2015;35(2):243–6.
22.
Wang J, Li L, Cheng H. Clinical Study on Xian-Lia-Jie-Du decoction combined With XELOX regimen in the treatment of stage iv colorectal cancer. Acta Chin Med Pharmacol. 2022;50(02):77–81.
23.
Du Y, Wan H, Huang P, Yang J, He Y. A critical review of Astragalus polysaccharides: from therapeutic mechanisms to pharmaceutics. Biomed Pharmacother. 2022;147:112654.PubMedCrossRef
24.
Jiang Y, Guo K, Wang P, Zhu Y, Huang J, Ruan S. The antitumor properties of atractylenolides: molecular mechanisms and signaling pathways. Biomed Pharmacother. 2022;155:113699.PubMedCrossRef
25.
El-Saadony MT, Yang T, Korma SA, Sitohy M, Abd El-Mageed TA, Selim S, et al. Impacts of turmeric and its principal bioactive curcumin on human health: pharmaceutical, medicinal, and food applications: a comprehensive review. Front Nutr. 2022;9:1040259.PubMedCrossRef
26.
Jia J, Li X, Ren X, Liu X, Wang Y, Dong Y, et al. Sparganii Rhizoma: a review of traditional clinical application, processing, phytochemistry, pharmacology, and toxicity. J Ethnopharmacol. 2021;268: 113571.PubMedCrossRef
27.
Huang Y, Zhu J, Lin X, Hong Y, Feng Y, Shen L. Potential of fatty oils from traditional chinese medicine in cancer therapy: a review for phytochemical, pharmacological and clinical studies. Am J Chin Med. 2019;47(4):727–50.PubMedCrossRef
28.
He L, Zhong Z, Chen M, Liang Q, Wang Y, Tan W. Current advances in coptidis rhizoma for gastrointestinal and other cancers. Front Pharmacol. 2021;12: 775084.PubMedCrossRef
29.
Sun P, Zhao W, Wang Q, Chen L, Sun K, Zhan Z, et al. Chemical diversity, biological activities and Traditional uses of and important Chinese herb Sophora. Phytomedicine. 2022;100: 154054.PubMedCrossRef
30.
Wen S, Zhang X, Wu Y, Yu S, Zhang W, Liu D, et al. Agrimonia pilosa Ledeb.: a review of its traditional uses, botany, phytochemistry, pharmacology, and toxicology. Heliyon. 2022;8(8):e09972.PubMedPubMedCentralCrossRef
31.
Chan AW, Tetzlaff JM, Gøtzsche PC, Altman DG, Mann H, Berlin JA, et al. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ (Clinical research ed). 2013;346: e7586.PubMed
32.
Linde K, Brinkhaus B. Randomized trials of Chinese herbal medicine: a new extension of the CONSORT statement. Ann Intern Med. 2017;167(2):133–4.PubMedCrossRef
33.
Li Z, Shi Q, Liu M, Jia L, He B, Yang Y, et al. Validation and Application of the MD Anderson Symptom Inventory for Traditional Chinese Medicine (MDASI-TCM). J Natl Cancer Inst Monogr. 2017;2017(52).
34.
Zheng R, Zhang S, Zeng H, Wang S, Sun K, Chen R, et al. Cancer incidence and mortality in China, 2016. J Natl Cancer Center. 2022;2(1):1–9.CrossRef
35.
36.
Rothwell P, Wilson M, Elwin C, Norrving B, Algra A, Warlow C, et al. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet (London, England). 2010;376(9754):1741–50.PubMedCrossRef
37.
Algra A, Rothwell P. Effects of regular aspirin on long-term cancer incidence and metastasis: a systematic comparison of evidence from observational studies versus randomised trials. Lancet Oncol. 2012;13(5):518–27.PubMedCrossRef
38.
Rothwell P, Wilson M, Price J, Belch J, Meade T, Mehta Z. Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials. Lancet (London, England). 2012;379(9826):1591–601.PubMedCrossRef
39.
Domingo E, Church D, Sieber O, Ramamoorthy R, Yanagisawa Y, Johnstone E, et al. Evaluation of PIK3CA mutation as a predictor of benefit from nonsteroidal anti-inflammatory drug therapy in colorectal cancer. J Clin Oncol. 2013;31(34):4297–305.PubMedCrossRef
40.
Meyerhardt JA, Shi Q, Fuchs CS, Meyer J, Niedzwiecki D, Zemla T, et al. Effect of celecoxib vs placebo added to standard adjuvant therapy on disease-free survival among patients with stage iii colon cancer: the CALGB/SWOG 80702 (Alliance) randomized clinical trial. JAMA. 2021;325(13):1277–86.PubMedPubMedCentralCrossRef
41.
Morales-Oyarvide V, Meyerhardt JA, Ng K. Vitamin D and physical activity in patients with colorectal cancer: epidemiological evidence and therapeutic implications. Cancer journal (Sudbury, Mass). 2016;22(3):223–31.PubMedCrossRef
42.
Fuchs M, Yuan C, Sato K, Niedzwiecki D, Ye X, Saltz L, et al. Predicted vitamin D status and colon cancer recurrence and mortality in CALGB 89803 (Alliance). Ann Oncol. 2017;28(6):1359–67.PubMedPubMedCentralCrossRef
43.
Urashima M, Ohdaira H, Akutsu T, Okada S, Yoshida M, Kitajima M, et al. Effect of Vitamin D supplementation on relapse-free survival among patients with digestive tract cancers: The AMATERASU randomized clinical trial. JAMA. 2019;321(14):1361–9.PubMedPubMedCentralCrossRef
44.
Mc Menamin ÚC, Murray LJ, Hughes CM, Cardwell CR. Metformin use and survival after colorectal cancer: a population-based cohort study. Int J Cancer. 2016;138(2):369–79.PubMedCrossRef
45.
Du L, Wang M, Kang Y, Li B, Guo M, Cheng Z, et al. Prognostic role of metformin intake in diabetic patients with colorectal cancer: an updated qualitative evidence of cohort studies. Oncotarget. 2017;8(16):26448–59.PubMedPubMedCentralCrossRef
46.
Vernieri C, Galli F, Ferrari L, Marchetti P, Lonardi S, Maiello E, et al. Impact of metformin use and diabetic status during adjuvant fluoropyrimidine-oxaliplatin chemotherapy on the outcome of patients with resected colon cancer: a TOSCA Study subanalysis. Oncologist. 2019;24(3):385–93.PubMedPubMedCentralCrossRef
47.
Christou N, Bergen E, Canton C, Le Malicot K, Di Bartolomeo M, Galli F, et al. Impact of diabetes and metformin use on recurrence and outcome in stage II-III colon cancer patients-A pooled analysis of three adjuvant trials. Eur J Cancer (Oxford, England : 1990). 2022;166:100–11.
48.
McQuade JL, Meng Z, Chen Z, Wei Q, Zhang Y, Bei W, et al. Utilization of and attitudes towards traditional Chinese medicine therapies in a Chinese cancer hospital: a survey of patients and physicians. evidence-based complementary and alternative medicine : eCAM. 2012;2012: 504507.PubMedCrossRef
49.
Chen G, Qiao TT, Ding H, Li CX, Zheng HL, Chen XL, et al. Use of Chinese herbal medicine therapies in comprehensive hospitals in central China: a parallel survey in cancer patients and clinicians. Journal of Huazhong University of Science and Technology Medical sciences = Hua zhong ke ji da xue xue bao Yi xue Ying De wen ban = Huazhong keji daxue xuebao Yixue Yingdewen ban. 2015;35(6):808–14.
50.
Lv J, Jia Y, Li J, Kuai W, Li Y, Guo F, et al. Gegen Qinlian decoction enhances the effect of PD-1 blockade in colorectal cancer with microsatellite stability by remodelling the gut microbiota and the tumour microenvironment. Cell Death Dis. 2019;10(6):415.PubMedPubMedCentralCrossRef
51.
Huang S, Peng W, Mao D, Zhang S, Xu P, Yi P, et al. Kangai Injection, a traditional Chinese medicine, improves efficacy and reduces toxicity of chemotherapy in advanced colorectal cancer patients: a systematic review and meta-analysis. Evidence-based complementary and alternative medicine : eCAM. 2019;2019:8423037.PubMedCrossRef
52.
Sun L, Yan Y, Chen D, Yang Y. Quxie capsule modulating gut microbiome and its association with t cell regulation in patients with metastatic colorectal cancer: result from a randomized controlled clinical trial. Integr Cancer Ther. 2020;19:1534735420969820.PubMedPubMedCentralCrossRef
53.
Dai Y, Wang H, Sun R, Diao J, Ma Y, Shao M, et al. Modified Shenlingbaizhu decoction represses the pluripotency of colorectal cancer stem cells by inhibiting TGF-β mediated EMT program. Phytomedicine. 2022;103:154234.PubMedCrossRef
54.
Yu C, Chen T, Lu S, Hu W, Zhang Q, Tan J, et al. Identification of significant modules and targets of Xian-Lian-Jie-Du decoction based on the analysis of transcriptomics, proteomics and single-cell transcriptomics in colorectal tumor. J Inflamm Res. 2022;15:1483–99.PubMedPubMedCentralCrossRef
55.
Zhang Q, Cheng H, Yu C, Shen W, Xu C, Tan J, et al. Effect of Xianlian Jiedu formula on intestinal cell types in colorectalcancer model mice with damp-heat stasis toxin pattern. J Tradit Chin Med. 2022;63(05):461–7.
56.
Chen T, Yu C, Xu H, Cheng H, Shen W, Tan J, et al. Transcriptome analysis of Xianlian Jiedu prescription in intervention of colorectalcarcinoma due to dampness, heat, stasis, and toxin in mice. Chin J Exp Tradit Med Formulae. 2022;28(08):63–71.
57.
Shao C, Zuo Q, Lin J, Yu RJ, Fu Y, Xiao M, et al. Effect of Chinese herbal medicine on the survival of colorectal cancer patients with liver-limited metastases: a retrospective cohort study, 2008 to 2017. Integr Cancer Ther. 2019;18:1534735419883687.PubMedPubMedCentralCrossRef
Metadata
Title
Efficacy and safety of Xian-Lian-Jie-Du optimization decoction as an adjuvant treatment for prevention of recurrence in patients with stage IIIB/IIIC colon cancer: study protocol for a multicentre, randomized controlled trial
Authors
Xuechen Geng
Ziqiang Wang
Li Feng
Yanhong Gu
Renjie Wang
Qinghua Yao
Yangxian Xu
Jianyu Wu
Zhiwei Jiang
Kai Chen
Wenwei Hu
Dongxin Tang
Jiege Huo
Ling Li
Qianqian Bu
Shuoqi Zhao
Bei Zhang
Haibo Cheng
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2023
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-023-04052-2

Other articles of this Issue 1/2023

BMC Complementary Medicine and Therapies 1/2023 Go to the issue

Research

The effect of lemon inhalation aromatherapy on pain, nausea, as well as vomiting and neurovascular assessment in patients for lower extremity fracture surgery: a randomized trial

Research

Computational biology and in vitro studies for anticipating cancer-related molecular targets of sweet wormwood (Artemisia annua)

Research

Pharmacotechnical aspects of a stable probiotic formulation toward multidrug-resistance antibacterial activity: design and quality control

Research

Efficacy and safety of Obex® in overweight and obese subjects: a randomised, double-blind, placebo-controlled clinical trial

Research

Therapeutic effects of resveratrol and Omega-3 in mice atherosclerosis: focus on histopathological changes

Correction

Correction: Gut microbiota mediated the therapeutic efficiency of Simiao decoction in the treatment of gout arthritis mice