Analysis of Clinical Trials Using Anti-Tumor Traditional Chinese Medicine Monomers

Overview

Journal Drug Des Devel Ther

Specialty Pharmacology

Date 2024 Jun 10

PMID 38855536

Authors

Dan Lv

Yuling Liu

Ruying Tang

Sai Fu

Shasha Kong

Qian Liao

Hui Li

Longfei Lin

Affiliations

Soon will be listed here.

Abstract

The potential anti-cancer effect of traditional Chinese medicine (TCM) monomers has been widely studied due to their advantages of well-defined structure, clear therapeutic effects, and easy quality control during the manufacturing process. However, clinical trial information on these monomers is scarce, resulting in a lack of knowledge regarding the research progress, efficacy, and adverse reactions at the clinical stage. Therefore, this study systematically reviewed the clinical trials on the anti-cancer effect of TCM monomers registered in the Clinicaltrials.gov website before 2023.4.30, paying special attention to the trials on tumors, aiming to explore the research results and development prospects in this field. A total of 1982 trials were started using 69 of the 131 TCM monomers. The number of clinical trials performed each year showed an overall upward trend. However, only 26 monomers entered into 519 interventional anti-tumor trials, with vinblastine (194, 37.38%) and camptothecin (146, 28.13%) being the most used. A total of 45 tumors were studied in these 519 trials, with lymphoma (112, 21.58%) being the most frequently studied. Clinical trials are also unevenly distributed across locations and sponsors/collaborators. The location and the sponsor/collaborator with the highest number of performed trials were the United States (651,32.85%) and NIH (77). Therefore, China and its institutions still have large room for progress in promoting TCM monomers in anti-tumor clinical trials. In the next step, priority should be given to the improvement of the research and development ability of domestic enterprises, universities and other institutions, using modern scientific and technological means to solve the problems of poor water solubility and strong toxic and side effects of monomers, so as to promote the clinical research of TCM monomers.

References

Tse T, Fain K, Zarin D . How to avoid common problems when using ClinicalTrials.gov in research: 10 issues to consider. BMJ. 2018; 361:k1452. PMC: 5968400. DOI: 10.1136/bmj.k1452. View

Cortes J, Lipton J, Rea D, Digumarti R, Chuah C, Nanda N . Phase 2 study of subcutaneous omacetaxine mepesuccinate after TKI failure in patients with chronic-phase CML with T315I mutation. Blood. 2012; 120(13):2573-80. PMC: 4916583. DOI: 10.1182/blood-2012-03-415307. View

Zhou Y, Yang J, He Y, Lv Y, Wang C, Deng H . Characteristic analysis of clinical trials for new traditional Chinese medicines in mainland China from 2013 to 2021. Front Med (Lausanne). 2022; 9:1008683. PMC: 9622921. DOI: 10.3389/fmed.2022.1008683. View

Zhang Y, Qi X, Gong L, Li Y, Liu L, Xue X . Roles of reactive oxygen species and MAP kinases in the primary rat hepatocytes death induced by toosendanin. Toxicology. 2008; 249(1):62-8. DOI: 10.1016/j.tox.2008.04.005. View

Lu J, Liu C, Wang P, Ghazwani M, Xu J, Huang Y . The self-assembling camptothecin-tocopherol prodrug: An effective approach for formulating camptothecin. Biomaterials. 2015; 62:176-87. PMC: 4470812. DOI: 10.1016/j.biomaterials.2015.05.046. View

Sanoff H, Moon D, Moore D, Boles J, Bui C, Blackstock W . Phase I/II trial of nano-camptothecin CRLX101 with capecitabine and radiotherapy as neoadjuvant treatment for locally advanced rectal cancer. Nanomedicine. 2019; 18:189-195. PMC: 7881832. DOI: 10.1016/j.nano.2019.02.021. View

Xie H, Wang G, Lv H, Sun R, Jiang X, Li H . Development of a HPLC-MS assay for ginsenoside Rh2, a new anti-tumor substance from natural product and its pharacokinetic study in dogs. Eur J Drug Metab Pharmacokinet. 2005; 30(1-2):63-7. DOI: 10.1007/BF03226409. View

Li N, Feng L, Tan Y, Xiang Y, Zhang R, Yang M . Preparation, Characterization, Pharmacokinetics and Biodistribution of Baicalin-Loaded Liposome on Cerebral Ischemia-Reperfusion after i.v. Administration in Rats. Molecules. 2018; 23(7). PMC: 6100585. DOI: 10.3390/molecules23071747. View

Tsurutani J, Iwata H, Krop I, Janne P, Doi T, Takahashi S . Targeting HER2 with Trastuzumab Deruxtecan: A Dose-Expansion, Phase I Study in Multiple Advanced Solid Tumors. Cancer Discov. 2020; 10(5):688-701. PMC: 8292921. DOI: 10.1158/2159-8290.CD-19-1014. View

10.

Margulis V, Puligandla M, Trabulsi E, Plimack E, Kessler E, Matin S . Phase II Trial of Neoadjuvant Systemic Chemotherapy Followed by Extirpative Surgery in Patients with High Grade Upper Tract Urothelial Carcinoma. J Urol. 2019; 203(4):690-698. PMC: 7735436. DOI: 10.1097/JU.0000000000000644. View

11.

Tian X, Nguyen M, Foote H, Caster J, Roche K, Peters C . CRLX101, a Nanoparticle-Drug Conjugate Containing Camptothecin, Improves Rectal Cancer Chemoradiotherapy by Inhibiting DNA Repair and HIF1α. Cancer Res. 2016; 77(1):112-122. PMC: 5214961. DOI: 10.1158/0008-5472.CAN-15-2951. View

12.

Selas A, Martin-Encinas E, Fuertes M, Masdeu C, Rubiales G, Palacios F . A patent review of topoisomerase I inhibitors (2016-present). Expert Opin Ther Pat. 2021; 31(6):473-508. DOI: 10.1080/13543776.2021.1879051. View

13.

Schmidt K, Karzai F, Bilusic M, Cordes L, Chau C, Peer C . A Single-arm Phase II Study Combining NLG207, a Nanoparticle Camptothecin, with Enzalutamide in Advanced Metastatic Castration-resistant Prostate Cancer Post-Enzalutamide. Oncologist. 2022; 27(9):718-e694. PMC: 9438911. DOI: 10.1093/oncolo/oyac100. View

14.

Wang X, Yang C, Ru Y, Xie L, Xiao B, Jin X . An optimal combination of five main monomer components in Wuzi Yanzong Pill that prevents neural tube defects and reduces apoptosis and oxidative stress. J Ethnopharmacol. 2023; 313:116540. DOI: 10.1016/j.jep.2023.116540. View

15.

Zou M, Xu Y, Lin P, Zhou L, Xia X . Use of different ligand modification liposomes to evaluate the anti-liver tumor activity of cantharidin. J Liposome Res. 2023; 33(3):283-299. DOI: 10.1080/08982104.2022.2163254. View

16.

Zarin D, Tse T, Williams R, Califf R, Ide N . The ClinicalTrials.gov results database--update and key issues. N Engl J Med. 2011; 364(9):852-60. PMC: 3066456. DOI: 10.1056/NEJMsa1012065. View

17.

Li Y, Zeng Z, Chen D, Gu Z, Yan W, Yue L . Facilitated Drug Repurposing with Artemisinin-Derived PROTACs: Unveiling PCLAF as a Therapeutic Target. J Med Chem. 2023; 66(16):11335-11350. DOI: 10.1021/acs.jmedchem.3c00824. View

18.

Guo C, He J, Song X, Tan L, Wang M, Jiang P . Pharmacological properties and derivatives of shikonin-A review in recent years. Pharmacol Res. 2019; 149:104463. DOI: 10.1016/j.phrs.2019.104463. View

19.

Chen L, Wang J, Wu J, Zheng Q, Hu J . Indirubin suppresses ovarian cancer cell viabilities through the STAT3 signaling pathway. Drug Des Devel Ther. 2018; 12:3335-3342. PMC: 6174913. DOI: 10.2147/DDDT.S174613. View

20.

Gordon L, Hong F, Fisher R, Bartlett N, Connors J, Gascoyne R . Randomized phase III trial of ABVD versus Stanford V with or without radiation therapy in locally extensive and advanced-stage Hodgkin lymphoma: an intergroup study coordinated by the Eastern Cooperative Oncology Group (E2496). J Clin Oncol. 2012; 31(6):684-91. PMC: 3574266. DOI: 10.1200/JCO.2012.43.4803. View