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

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.

Keywords: adverse reactions; anti-cancer; interventional clinical trials; research progress; traditional Chinese medicine monomers.

Figure 1

The chemical structures of anti-tumor flavonoids with clinical trials data.

Figure 2

The chemical structures of anti-tumor alkaloids with clinical trials data.

Figure 3

The chemical structures of anti-tumor terpenoids with clinical trials data.

Figure 4

The chemical structures of anti-tumor phenolic compounds with clinical trials data.

Figure 5

The chemical structures of six other types of anti-tumor monomers with clinical trials data. The specific classification is as follows: 58–63 belong to phenylpropanoids; 64–65 belong to quinonoids; 66 belongs to polysaccharides; 67 belongs to steroid compounds; 68 belongs to macrocyclic ketone compounds and 69 belongs to inorganic salt compounds.

Figure 6

(a) Data collection and processing. The box on the left is about the search process and results of anti-tumor TCM monomers and The box on the right is about the search and inclusion criteria for clinical trials of anti-tumor TCM monomers. (b) Key types of clinical trials.

Figure 7

The number of interventional clinical trials at each phase.

Figure 8

The main indications and interventions of interventional trials.

Figure 9

(a) The enrollment of interventional trials. (b) The start date of interventional trials. (c) The status of interventional trials.

Figure 10

(a) Geographical distribution of clinical trials of TCM monomers registered by leading clinical trial units worldwide. (b) Locations with over 10 clinical trials.

Figure 11

(a) The number of interventional anti-tumor clinical trials of TCM monomers. (b) The number of interventional clinical trials involving different types of cancers. (c) The number of trials in each phase of interventional anti-cancer trials.