Current Characteristics of Herbal Medicine Interventions for Cancer on Clinical Databases: A Cross-Sectional Study
Cancer has been known as the primary cause of death worldwide. With the rapid increment of the aging population, cancer has become a major problem for health systems. The leading cause of cancer cases was breast cancer, accounting for 2.26 million cases; the most common cause of cancer death was lung cancer, accounting for 1.8 million deaths in 2020. As the number of cancer patients has been rising each year, various types of cancer care services have been introduced apart from chemo- and radiotherapies. There has been a growing number of patients seeking several modalities of complementary and alternative medicine (CAM) when coping with cancer. Among the therapies, herbal medicine therapy has been popular for improving physical symptoms, stimulating the immune system, improving mental health, etc. According to the World Health Organization (WHO) report, herbal medicine is defined as herbs, herbal preparations, and herbal finished products containing plant or inorganic ingredients. It is vital to note that the highest users of herbal medicines were known as cancer patients. Cancer patients with experience of herbal medicines have said that it relieves symptoms, improves adverse effects from conventional treatments for cancer, and prevents further recurrence or metastasis. According to a systematic review on the use of herbal supplements in the United Kingdom, 22% of cancer patients were taking herbal supplements for the purpose of treating symptoms and improving quality of life. Furthermore, the utilization of herbal medicines has received increasing attention as an auxiliary cancer treatment strategy from various countries for alleviating the side effects of chemotherapy or radiation while improving the overall quality of life of cancer patients. As a well-known example, herbal medicines showed positive results in treating gastrointestinal side effects of cancer patients, such as vomiting, diarrhea, constipation, and nausea. More importantly, combination therapies, using both herbal medicines and conventional drugs, to treat cancer and its related adverse effects have gained much attraction among researchers to maximize its effects. Even though numerous cancer patients are in favor of using herbal medicines to treat the adverse effects of cancer, there still is a paucity of evidence proving the positive effects of herbal medicine interventions for treating cancer. Exploring and analyzing registered clinical trials may be vital to assist future clinical practice, as clinical trials provide a reliable source of efficacy and safety. Additionally, it is the most widely used among researchers to find comprehensive information regarding completed or ongoing trials, identifying the characteristics of the registered trials in the fields or topics of interest. Hence, the aim of this cross-sectional study is to investigate the current status of the characteristic of registered trials using herbal medicine interventions for cancer via clinical databases.   Reporting Guideline As a cross-sectional study, this work was reported according to the STROBE guideline. Searching of Registered Trials ClinicalTrials.gov was first chosen since it is the largest clinical trial registry, with high transparency and free accessibility for detailed information on past and present clinical trials, which provides valid evidence of efficacy and safety for clinical practice. In order to ensure adequate coverage of the existing clinical trials, the ISRCTN registry, the Chinese clinical trial registry (ChiCTR), and the international clinical trials registry platform (ICTRP) were additionally chosen. The advanced search function was utilized along with the preliminary search terms, including (herbal medicine* OR phytotherap* OR herbal therap* OR botanical therap* OR botanical medicine* OR Chinese herbal OR plant extract* OR ethnobotany, ethnopharmacology, herbalism) AND (cancer OR neoplasm*OR tumor* OR oncology OR malignanc* OR tumor* OR carcinoma OR malignanc* OR neoplasia*) to find the most significant number of registered trials on March 26, 2023. Although the keyword “herbal medicine” and its similar words were utilized to locate trials using herbal medicines, this keyword strategy was intended not to survey all the literature of clinical trials on herbs for cancer. Inclusion and Exclusion Criteria The searched results from each database were exported and tailored in CSV file format. All trials were included inception to the search date with the keyword strategy, presuming that there were limited trials using herbal medicines. The trials not related to herbal compounds or herbal medicines, trials not related to cancer patients, terminated or suspended trials, and non-clinical trials, such as questionnaire survey studies, were excluded. Further, the final chosen trials were checked via PubMed, Google Scholar, SCOPUS, and Chinese National Knowledge Infrastructure (CNKI) database to locate any publications that may have results. Three authors (BY, SY, and SK) individually reviewed all trials regarding herbal medicine interventions. If there were any disagreements during the inclusion and exclusion process, other authors (JK, JI, and JL) were invited to reach a consensus. Data Extraction and Statistical Analysis The following accessible data of all clinical trials were extracted from the searched results: database number, title, status, study results, conditions, outcome measures, lead sponsors, gender, age, phases, enrollment, primary funding, study type, all available study designs, start date, completion date, results posted, location, and URL. The final dataset was imported to Microsoft Excel 2019 software to perform descriptive analysis, and the categorial data were reported as frequency and percentage.   As a cross-sectional study, this work was reported according to the STROBE guideline.   ClinicalTrials.gov was first chosen since it is the largest clinical trial registry, with high transparency and free accessibility for detailed information on past and present clinical trials, which provides valid evidence of efficacy and safety for clinical practice. In order to ensure adequate coverage of the existing clinical trials, the ISRCTN registry, the Chinese clinical trial registry (ChiCTR), and the international clinical trials registry platform (ICTRP) were additionally chosen. The advanced search function was utilized along with the preliminary search terms, including (herbal medicine* OR phytotherap* OR herbal therap* OR botanical therap* OR botanical medicine* OR Chinese herbal OR plant extract* OR ethnobotany, ethnopharmacology, herbalism) AND (cancer OR neoplasm*OR tumor* OR oncology OR malignanc* OR tumor* OR carcinoma OR malignanc* OR neoplasia*) to find the most significant number of registered trials on March 26, 2023. Although the keyword “herbal medicine” and its similar words were utilized to locate trials using herbal medicines, this keyword strategy was intended not to survey all the literature of clinical trials on herbs for cancer.   The searched results from each database were exported and tailored in CSV file format. All trials were included inception to the search date with the keyword strategy, presuming that there were limited trials using herbal medicines. The trials not related to herbal compounds or herbal medicines, trials not related to cancer patients, terminated or suspended trials, and non-clinical trials, such as questionnaire survey studies, were excluded. Further, the final chosen trials were checked via PubMed, Google Scholar, SCOPUS, and Chinese National Knowledge Infrastructure (CNKI) database to locate any publications that may have results. Three authors (BY, SY, and SK) individually reviewed all trials regarding herbal medicine interventions. If there were any disagreements during the inclusion and exclusion process, other authors (JK, JI, and JL) were invited to reach a consensus.   The following accessible data of all clinical trials were extracted from the searched results: database number, title, status, study results, conditions, outcome measures, lead sponsors, gender, age, phases, enrollment, primary funding, study type, all available study designs, start date, completion date, results posted, location, and URL. The final dataset was imported to Microsoft Excel 2019 software to perform descriptive analysis, and the categorial data were reported as frequency and percentage.   The initial search yielded 169 registered trials on the aforementioned databases. With the keyword search strategy, a total of 154 trials were available for review. After the exclusion criteria process, 102 trials remained for analysis . General Characteristics of Included Trials The characteristics of the included trials are shown in . The largest number of trials were initiated between 2016 and 2020, with 36 trials (35.29%) in this period. Although 45 trials (44.12%) were completed, only 8 trials (7.84%) were indicated to have results. Asia was the most frequently identified study location (N = 64, 62.75%), followed by North America (N = 21, 20.59%). Most of the primary funding came from other funding sources (N = 82, 80.39%). Hospitals have sponsored the most trials (N = 43, 42.16%). Most trials had participants ages 18 and older; however, 4 trials included child participants (3.92%). Study Designs of Included Trials Most trials were found to be interventional (N = 94, 92.16%) and in phase II (N = 29, 28.43%). The primary purpose of the trials was treatment (N = 71, 69.61%), followed by supportive care (N = 18, 17.65%). The majority of the trials were randomized (N = 69, 67.65%), and most trials’ anticipated enrollment was less than 100 (N = 66, 64.71%). Most trials had a double-arm design (N = 63, 61.76%), and parallel assignment (N = 72, 70.59%) was used the most as an interventional model. Less than half of the trials were masked; single, double, and quadruple masking was used the most among the trials. The details of all study designs are shown in . Description of Herbal Medicines in Various Cancer Types of Included Trials The cancer types of the included trials are shown in . Cancer types adopted for clinical trials were mostly concentrated on breast cancer, followed by lung cancer and non-specified cancer. According to , all of the utilized herbal medicines were categorized into 16 different conditions in clinical trials. In addition, herbal medicines adopted for clinical trials were mostly concentrated on the decoction of herbal mixtures; lung cancer trials were found to have well-known prescriptions the most frequently. It is noteworthy that various herbal combinations of herbal mouthwash, oil, and tea were used for trials. YangYinFang, YiQi Fang, and YiQi Yang Yin Fang were most adopted in lung cancer trials. Traditional Chinese medicines were most applied to breast cancer; however, the majority of the trials did not reveal the actual descriptions of the prescriptions. PHY906 (KD018) has appeared most in colorectal cancer trials. PHY906 commonly appeared in hepatocellular carcinoma and colorectal cancer. Characteristics of Completed Trials With Final Results Of the 102 trials, only 8 trials reported results on the website. Six trials started between 2004 and 2009; 2 trials began in 2013 and 2014, respectively. One trial published a meeting abstract (NCT00411762), and four trials had publications (NCT00730158, NCT02638051, ISRCTN7208885, ChiCTR-TRC-10001017). - Six trials investigated herbal medicines as adjuvant therapy in combination with conventional therapy, and 2 trials tested single therapy. Four trials recruited more than 50 participants, and the other 4 recruited less than 50 participants. The highest number of recruited patients was 260. One of the trials, NCT00243022, was terminated due to low patient accrual even though it is indicated as “has results” via ClinicalTrials.gov. NCT00411762 concluded that a combination of capecitabine and PHY906 is safe for patients with solid tumors; the combination of cationic anti-microbial peptides and PHY906 has also shown insufficient evidence in patients with solid tumors for its effectiveness. The results of NCT00622440 indicated that Arnebia Indigo Jade Pearl (AIJP) cream showed a better clinical response for treatment of precancerous anal lesions in order to prevent their progression to anal cancer. AIJP is a multiherbal topical cream based on Chinese herbal medicine (CHM) that has been specifically designed to treat people with the cancer precursor lesions caused by human papillomavirus. NCT00730158 showed that KD018 (traditional Chinese medicine formulation) relieves the gastrointestinal toxicity of irinotecan in patients with metastatic colorectal cancer. NCT02638051 reported that Shi Pi (TCM herbal decoction) combined with modulated electro-hyperthermia is safe and tolerable in patients with malignant ascites; it was found that the intervention group had a higher level of quality of life than the control group, yet adverse effects such as bone marrow depression might become an issue. According to the trial, Shi Pi decoction invigorates the spleen, promotes qi circulation to induce diuresis and treat foot-taiyin meridian in Gu Zhang. NCT01898091 used the herbal mouth rinse for adults with head and neck cancer receiving radiation therapy, testing whether the study mouth rinse may lessen oral mucositis. Unfortunately, the trial study indicated that there is not an agreement between principal investigators and the sponsor to discuss or publish trial results after the trial is completed. ISRCTN7208885 concluded that administering medicinal cannabis with either irinotecan or docetaxel did not have much impact on pharmacokinetics of the drugs. ChiCTR-TRC-10001017 noted that after 2 cycles of maintenance TCM treatment, the serum concentration of sCTLA-4 in patients with advanced NSCLC was significantly lower. The study indicated that controlling the serum concentration of sCTLA-4 may be a potential mechanism for TCM maintenance treatment of NSCLC drugs. Further exploration was carried out to locate more publications of the final trials despite the indication as “has no results” on trial databases since researchers may have been delayed in updating the results. As mentioned, the extra search was discovered via PubMed, Google Scholar, SCOPUS, and CNKI and found 8 more publications. Among the 8 publications, only one was published as a meeting abstract (NCT00669656), and others were journal articles (NCT02795390, NCT02468141, NCT00076609, NCT03911921, NCT02900742, IRCT20180722040556N2, IRCT20180722040556N1). - The highest number of enrolled participants was 83; the lowest was 32. Only 2 studies (NCT00669656, NCT00076609) used the single-arm design, having the intervention group, while all others used the double-arm. Four studies (NCT00076609, NCT02900742, IRCT20180722040556N2, IRCT20180722040556N1) investigated herbal medicines as adjuvant therapy combined with conventional treatment, and the rest utilized herbal medicine only. The complete list of the results of the trials is summarized in . NCT00669656 concluded that the prostate health cocktail had decreased the prostate-specific antigen level by 37% of the patients who experienced biochemically recurrent prostate cancer. NCT02795390 suggested that a modified traditional Chinese herbal formula, MaZiRenWan, was effective for relieving constipation in patients in palliative cancer care. NCT02468141 indicated SDT could be a potential option for anorexia management in cancer patients, showing improvement in both anorexia and quality of life. NCT00076609 mentioned that PHY906, a pharmaceutical-grade formulation of 4 traditional Chinese herbs, increased the index of capecitabine by enhancing its antitumor activity while reducing toxicity in advanced hepatocellular carcinoma. NCT03911921 appeared that RSYRT, also known as ChongGuanYaoYe in TCM, for reducing cancer-related fatigue was found to be effective. Regarding the trial of NCT02900742, the intervention group (chemotherapy with Chinese herbal medicine formula) showed significant improvements in progression-free survival rate and relieved symptoms while improving overall quality of life. IRCT20180722040556N2 and IRCT20180722040556N1 have shown effectiveness in preventing weight loss and improving appetite for advanced cancer patients. , Both trials used megestrol with an herbal combination in the intervention group; the type of herbal combination was unknown.   The characteristics of the included trials are shown in . The largest number of trials were initiated between 2016 and 2020, with 36 trials (35.29%) in this period. Although 45 trials (44.12%) were completed, only 8 trials (7.84%) were indicated to have results. Asia was the most frequently identified study location (N = 64, 62.75%), followed by North America (N = 21, 20.59%). Most of the primary funding came from other funding sources (N = 82, 80.39%). Hospitals have sponsored the most trials (N = 43, 42.16%). Most trials had participants ages 18 and older; however, 4 trials included child participants (3.92%).   Most trials were found to be interventional (N = 94, 92.16%) and in phase II (N = 29, 28.43%). The primary purpose of the trials was treatment (N = 71, 69.61%), followed by supportive care (N = 18, 17.65%). The majority of the trials were randomized (N = 69, 67.65%), and most trials’ anticipated enrollment was less than 100 (N = 66, 64.71%). Most trials had a double-arm design (N = 63, 61.76%), and parallel assignment (N = 72, 70.59%) was used the most as an interventional model. Less than half of the trials were masked; single, double, and quadruple masking was used the most among the trials. The details of all study designs are shown in .   The cancer types of the included trials are shown in . Cancer types adopted for clinical trials were mostly concentrated on breast cancer, followed by lung cancer and non-specified cancer. According to , all of the utilized herbal medicines were categorized into 16 different conditions in clinical trials. In addition, herbal medicines adopted for clinical trials were mostly concentrated on the decoction of herbal mixtures; lung cancer trials were found to have well-known prescriptions the most frequently. It is noteworthy that various herbal combinations of herbal mouthwash, oil, and tea were used for trials. YangYinFang, YiQi Fang, and YiQi Yang Yin Fang were most adopted in lung cancer trials. Traditional Chinese medicines were most applied to breast cancer; however, the majority of the trials did not reveal the actual descriptions of the prescriptions. PHY906 (KD018) has appeared most in colorectal cancer trials. PHY906 commonly appeared in hepatocellular carcinoma and colorectal cancer.   Of the 102 trials, only 8 trials reported results on the website. Six trials started between 2004 and 2009; 2 trials began in 2013 and 2014, respectively. One trial published a meeting abstract (NCT00411762), and four trials had publications (NCT00730158, NCT02638051, ISRCTN7208885, ChiCTR-TRC-10001017). - Six trials investigated herbal medicines as adjuvant therapy in combination with conventional therapy, and 2 trials tested single therapy. Four trials recruited more than 50 participants, and the other 4 recruited less than 50 participants. The highest number of recruited patients was 260. One of the trials, NCT00243022, was terminated due to low patient accrual even though it is indicated as “has results” via ClinicalTrials.gov. NCT00411762 concluded that a combination of capecitabine and PHY906 is safe for patients with solid tumors; the combination of cationic anti-microbial peptides and PHY906 has also shown insufficient evidence in patients with solid tumors for its effectiveness. The results of NCT00622440 indicated that Arnebia Indigo Jade Pearl (AIJP) cream showed a better clinical response for treatment of precancerous anal lesions in order to prevent their progression to anal cancer. AIJP is a multiherbal topical cream based on Chinese herbal medicine (CHM) that has been specifically designed to treat people with the cancer precursor lesions caused by human papillomavirus. NCT00730158 showed that KD018 (traditional Chinese medicine formulation) relieves the gastrointestinal toxicity of irinotecan in patients with metastatic colorectal cancer. NCT02638051 reported that Shi Pi (TCM herbal decoction) combined with modulated electro-hyperthermia is safe and tolerable in patients with malignant ascites; it was found that the intervention group had a higher level of quality of life than the control group, yet adverse effects such as bone marrow depression might become an issue. According to the trial, Shi Pi decoction invigorates the spleen, promotes qi circulation to induce diuresis and treat foot-taiyin meridian in Gu Zhang. NCT01898091 used the herbal mouth rinse for adults with head and neck cancer receiving radiation therapy, testing whether the study mouth rinse may lessen oral mucositis. Unfortunately, the trial study indicated that there is not an agreement between principal investigators and the sponsor to discuss or publish trial results after the trial is completed. ISRCTN7208885 concluded that administering medicinal cannabis with either irinotecan or docetaxel did not have much impact on pharmacokinetics of the drugs. ChiCTR-TRC-10001017 noted that after 2 cycles of maintenance TCM treatment, the serum concentration of sCTLA-4 in patients with advanced NSCLC was significantly lower. The study indicated that controlling the serum concentration of sCTLA-4 may be a potential mechanism for TCM maintenance treatment of NSCLC drugs. Further exploration was carried out to locate more publications of the final trials despite the indication as “has no results” on trial databases since researchers may have been delayed in updating the results. As mentioned, the extra search was discovered via PubMed, Google Scholar, SCOPUS, and CNKI and found 8 more publications. Among the 8 publications, only one was published as a meeting abstract (NCT00669656), and others were journal articles (NCT02795390, NCT02468141, NCT00076609, NCT03911921, NCT02900742, IRCT20180722040556N2, IRCT20180722040556N1). - The highest number of enrolled participants was 83; the lowest was 32. Only 2 studies (NCT00669656, NCT00076609) used the single-arm design, having the intervention group, while all others used the double-arm. Four studies (NCT00076609, NCT02900742, IRCT20180722040556N2, IRCT20180722040556N1) investigated herbal medicines as adjuvant therapy combined with conventional treatment, and the rest utilized herbal medicine only. The complete list of the results of the trials is summarized in . NCT00669656 concluded that the prostate health cocktail had decreased the prostate-specific antigen level by 37% of the patients who experienced biochemically recurrent prostate cancer. NCT02795390 suggested that a modified traditional Chinese herbal formula, MaZiRenWan, was effective for relieving constipation in patients in palliative cancer care. NCT02468141 indicated SDT could be a potential option for anorexia management in cancer patients, showing improvement in both anorexia and quality of life. NCT00076609 mentioned that PHY906, a pharmaceutical-grade formulation of 4 traditional Chinese herbs, increased the index of capecitabine by enhancing its antitumor activity while reducing toxicity in advanced hepatocellular carcinoma. NCT03911921 appeared that RSYRT, also known as ChongGuanYaoYe in TCM, for reducing cancer-related fatigue was found to be effective. Regarding the trial of NCT02900742, the intervention group (chemotherapy with Chinese herbal medicine formula) showed significant improvements in progression-free survival rate and relieved symptoms while improving overall quality of life. IRCT20180722040556N2 and IRCT20180722040556N1 have shown effectiveness in preventing weight loss and improving appetite for advanced cancer patients. , Both trials used megestrol with an herbal combination in the intervention group; the type of herbal combination was unknown.   Cancer patients have recently been utilizing CAM modalities, including herbal medicine therapy, for treating cancer and improving patients’ quality of life. The present cross-sectional study investigated the current status of herbal medicine interventions for cancer by analyzing registered clinical trials since there has been a lack of the characteristics of the registered trials. Thus, this may be the first study to report registered trials in such field. As the global herbal medicine market grew rapidly, the consumption of herbal medicine has also up-surged. Herbal medicines have been applied to cancer patients to relieve symptoms and improving adverse effects from conventional therapies, including chemotherapy and immunotherapy. , Several studies reported that herbal therapy for cancer patients is applied to treat cancer and anorexia, cachexia, insomnia, neuropathic pain, nausea, vomiting, and so on. - Meanwhile, misuse of herbal medicine can be harmful for cancer patients. Hence, it is essential to detect the gradually increasing registered trials regarding the use of herbal medicines in the field of cancer research. It is also vital to note that most trials were focused on treatment. According to a recent systematic review, including 155 studies and 809 065 participants, a large percentage of cancer patients sought herbal medicine during the course of conventional therapy, and the prevalence of herbal medicine use by cancer patients worldwide was 22%. Moreover, the use of traditional and complementary medicine in Europe by cancer patients has been high, varying from 44.7% to 72%. - As an example, a multi-institutional cohort study with long-term use of CHM in patients with esophageal cancer stage 4 found that patients with CHM had a higher 5-year survival rate than those without CHM, and the risk of death was also 46% lower than those without CHM. The rapid growth of cancer patients seeking herbal medicine therapies, may have occurred in part due to the synergistic combination of herb-drug interactions. For example, the combination treatment of gemcitabine, a chemical used in the treatment of pancreatic cancer, and C5E, an herbal mixture extract, has been found to be more effective than individual treatments since the mRNA expression levels of sonic hedgehog, which is implicated in the development of types of cancer, were downregulated when the co-treatment with C5E and gemcitabine was compared with the treatment with either C5E or gemcitabine alone. Herbal/dietary supplements (HDS) are the most popular CAM treatment among cancer patients. According to a survey, 127 out of 375 patients used HDS before and after a cancer diagnosis, and most patients stated that other drugs were used at the same time as HDS. Moreover, herbal medicine has positive effects, such as inhibiting tumor growth and cancer cell metastasis by inducing tumor cell apoptosis and reversing the resistance of existing chemotherapy drugs; therefore, adjuvant herbal treatment can make chemotherapy treatment more effective and less toxic than traditional chemotherapy drugs. Various modalities of CAM therapies have been known to be helpful for cancer patients. Among the trials, 2 trials (NCT04584775, ChiCTR2000038393) indicated that herbal medicines were combined with acupuncture, and 2 more trials (ChiCTR2000037192, ChiCTR-INR-16009557) also mentioned that herbal medicines were combined with moxibustion. According to a recent comprehensive narrative review regarding using CAM treatments for cancer pain, the study stated that a multimodal approach to cancer pain management, including herbal medicines, might improve the quality of pain treatment and patients’ quality of life. Moreover, a pilot study describes a multimodal outpatient complementary therapy program including herbs, conducted during adjuvant radiotherapy and/or chemotherapy or outpatient aftercare, showing its potential to improve the overall quality of life and reduce treatment-associated adverse effects. Regarding the final selection of trials from the databases, numerous trials were heavily concentrated on lung, breast, and colorectal cancer. According to cancer statistics 2022 by the America Cancer Society, the greatest number of cancer-related death are associated with lung cancer (21%), prostate cancer (11%), and colorectal cancer (9%) in men and with lung cancer (21%), breast cancer (15%) and colorectal cancer (8%) in women, which indicates that the selected trials seem to have focused on the types of cancer due to clinical needs. Furthermore, the herbal medicines utilized for clinical trials were mainly concentrated on the decoction of herbal mixtures. SH003 is a decoction of medicinal herbs consisting of Astragalus membranaceus, Angelica gigas, Trichosanthes Kirilowii. PHY906 is a decoction of a mixture of 4-herbs, Scutellarin baicalensis Georgi, Glycyrrhiza uralensis Fisch, Paeonia lactiflora Pall, and Ziziphus jujuba Mill. Besides, the aforementioned trials investigated DaHuang GanTsao Tang, Maekmoondong-tang, Xiang Bei Yang Rong Tang, Sheng-Yu-Tang, and others. Decoction is the most common form of administration of herbal medicine; formulas can be varied according to clinical need. When using decoctions, the herb-herb combined effect would act as multi-targeted in the clinical outcome. For instance, the decoction of Ephedra (Mahuang Tang et al ), which contains ephedra, cinnamon twig, bitter apricot seed, and licorice root, is used for its diaphoretic effect but also the relief of coughing and general aching during the common cold as well as reducing headaches. , With regard to the results of the published trials, 8 trials used combinations of chemotherapy and herbal medicine compared to 6 monotherapies only using herbal medicines. Notably, all the outcomes were positive among the trials that utilized the combined therapies. Considering the increasing popularity of herbal medicine among cancer patients, safety and effectiveness approaches to integrative cancer care remain undisclosed. According to a scoping review of pharmacoepidemiological studies based on real-world data on herb-drug interactions in cancer, most clinical interactions had no negative consequences. The study also stated that well-designed, multicenter, double-blind, and placebo-controlled randomized clinical trials are needed to elucidate the risks and benefits of using combined therapies. Another review further suggested it is imperative to seek more reliable evidence from other parts of the world, which provides an in-depth global perspective on herbal-drug combination therapy in cancer patients since most of the herbal medicine clinical trials are from Asia. Additionally, the essential potential for alleviating adverse events of chemotherapies was recognized; the outcomes from the published articles have revealed to prevent weight loss, reduce fatigue, and improve overall quality of life. A recent systematic review regarding using East Asian herbal medicine in cancer patients identified that combined therapies may benefit patients with cancer pain by increasing the response rate, relieving pain intensity, improving pain-related performance status, and improving quality of life. Several researchers and industry professionals have requested that a transparent scientific verification of traditional herbal medicines be needed to ensure safety and efficacy. Based on the gathered data via ClinicalTrials.gov, the ISRCTN registry, the ChiCTR, and the ICTRP, more trials are still required to provide evidence for clinical practice. However, it is vital to note the upward trajectory of the number of clinical trial registrations during the survey period. It is also noteworthy that the majority of the trials are in Phase 2. Although herbal medicine has long been used in practice, there always has been a lack of scientifically proven therapeutic effects and safety. This phenomenon perhaps may be associated with various challenges. First, the treatments in herbal medicines are complex, consisting of a mixture of active components and difficult-to-define inclusion and exclusion criteria. Randomized controlled trials (RCT) are usually double-blinded; however, it may be challenging to maintain double-blind when herbal treatment involves a multidimensional approach to prescribing herbal medicines. In addition, the selection of herbal medicine for the control group may also be challenging as the medicines somewhat closely match with the intervention group in order to provide evidence of a specific effect; however, it is incredibly arduous to match the standardized herbal medicines which have the credibility of the treatment to the patient in the similar clinical setting as the intervention group. This study has several limitations. First, all clinical trial data were only obtained from ClinicalTrials.gov, the ISRCTN registry, the ChiCTR, and the ICTRP; some missed clinical trials may have been registered in other registries. However, ClinicalTrials.gov does contain most global trials. Second, the search term “herbal medicine” does not retrieve every registered herbal medicine trial since some trials may have used the names of herbal extract and herbal decoction. Most of the single and multi-herbal trials registered in registries can only be retrieved by searching on the name of the plant, not with the “herbal medicine” search term. - Third, most of the trials are interventional trials so that observational trials might have been registered with other databases. Additional information on study protocols and in-depth results details may serve as valuable information for clinicians and researchers to further scrutinize the factors for using herbal medicine for cancer patients. As a general limitation of a clinical registry, the data quality of each trial may vary.   This cross-sectional study comprehensively analyzed the characteristics of the registered clinical trials related to herbal medicine and cancer via ClinicalTrials.gov, the ISRCTN registry, the ChiCTR, and the ICTRP. Most clinical trials were interventional studies in phase 2. Unsurprisingly, the highest number of trials were registered in Asia since traditional, complementary, and alternative medicine has been widely practiced for a long time. Almost half of the trials were found to be still ongoing, and only 16 trials had complete results for further analysis. Based on the results of the analysis, herbal medicines were primarily used for lung, breast, and colorectal cancer; however, this may change as more complete results are to be added in the near future. Overall, it can be assumed that an herbal medicine therapy will be another potential option to consider for healthcare professionals; the combination of herbal medicine and chemotherapy has attracted attention in the medical community due to various synergies. More importantly, there is not enough research solely using herbal medicine for treating cancer, it may be significant to design well-established study protocols to generate more concrete evidence for the cancer community.   sj-docx-2-ict-10.1177_15347354231218255 – Supplemental material for Current Characteristics of Herbal Medicine Interventions for Cancer on Clinical Databases: A Cross-Sectional Study Click here for additional data file. Supplemental material, sj-docx-2-ict-10.1177_15347354231218255 for Current Characteristics of Herbal Medicine Interventions for Cancer on Clinical Databases: A Cross-Sectional Study by Bo-Young Youn, Ji-Hyun Kim, Yong-Kyu Jo, Sanghoon Yoon, Ji-Yeong Im, Hyo-Jung Kim, Jae-Dong Lee and Seong-Gyu Ko in Integrative Cancer Therapies sj-xlsx-1-ict-10.1177_15347354231218255 – Supplemental material for Current Characteristics of Herbal Medicine Interventions for Cancer on Clinical Databases: A Cross-Sectional Study Click here for additional data file. Supplemental material, sj-xlsx-1-ict-10.1177_15347354231218255 for Current Characteristics of Herbal Medicine Interventions for Cancer on Clinical Databases: A Cross-Sectional Study by Bo-Young Youn, Ji-Hyun Kim, Yong-Kyu Jo, Sanghoon Yoon, Ji-Yeong Im, Hyo-Jung Kim, Jae-Dong Lee and Seong-Gyu Ko in Integrative Cancer Therapies   