Lingyun Sun, MD
Yufei Yang, MD
Guest Editor’s Note: Although guidelines recommend adjuvant combination chemotherapy for patients with stage II and III colon cancer who are at high risk of disease recurrence, fewer than 50% complete treatment because of fear of adverse effects or symptom burden. The herbal formula Jianpi Bushen is commonly used in China to alleviate chemotherapy-induced nausea and vomiting as well as myelosuppression. In this article, Lingyun Sun, MD, and Yufei Yang, MD, describe findings from their clinical trial of Jianpi Bushen in patients with stage III or high-risk stage II colon cancer receiving adjuvant chemotherapy.
Overview
It is estimated that colorectal cancer is the third leading cause of death globally.1 Oncology guidelines recommend adjuvant combination chemotherapy for patients with stage II and III colon cancer who are at high risk of disease recurrence and metastasis.2,3 However, fewer than 50% complete such treatment, with poor compliance correlated with negative survival outcomes.4,5 Major contributors to poor compliance include chemotherapy-induced adverse effects, symptom burden, and impaired quality of life.
Although antiemetics and hematopoietic factors have greatly improved the tolerability of chemotherapy, these agents may cause adverse events such as constipation, bone pain, and loss of appetite.6 A growing number of patients are seeking herbal medicine and supplements for symptom control and improvement of their overall well-being.7 Despite this trend, there is a lack of high-quality evidence supporting their use, and there are concerns over herb-drug interactions.
The Trial
We undertook a phase III randomized clinical trial to determine the effects of Jianpi Bushen, a traditional Chinese medicine formula, on chemotherapy completion and incidence of chemotherapy-induced adverse events in patients with stage II or III colon cancer receiving adjuvant CAPOX (capecitabine and oxaliplatin). A 12-herb formulation, Jianpi Bushen is part of standard care in traditional Chinese medicine hospitals and is used to manage chemotherapy-associated nausea and vomiting as well as myelosuppression.8
This multisite trial was conducted in 13 hospitals in China between August 2018 and December 2021.9 The trial included 400 patients with colon cancer (aged 18–80; stage III or high-risk stage II disease) who completed radical surgery within 6 weeks of enrollment and planned to undergo adjuvant chemotherapy with CAPOX. They were randomly assigned to receive Jianpi Bushen granules, taken orally twice daily, or placebo. The chemotherapy cycles and dosages were decided by the treating physicians at each of the 13 centers.
The primary outcome was the completion rate of planned chemotherapy. Secondary outcomes were the relative dose intensity of chemotherapy agents, symptom burden, and incidence of chemotherapy-related side effects.
Guest Editor
Jun J. Mao, MD, MSCE
Dr. Mao is the Laurance S. Rockefeller Chair in Integrative Medicine and Chief of Integrative Medicine Service at Memorial Sloan Kettering Cancer Center, New York.
Findings showed a significantly higher chemotherapy completion rate in the Jianpi Bushen vs placebo group (63.0% vs 47.6%; P = .003). The relative dose intensity of oxaliplatin was also higher in patients who received Jianpi Bushen (P = .049). Subgroup analyses revealed Jianpi Bushen to have significantly improved completion rates in high-risk stage II patients (73.0% vs 42.4%; P = .001) and in those aged 65 years or younger (66.9% vs 48.8%; P = .004). In addition, compared with placebo, the formula reduced grade ≥ 2 vomiting (3.8% vs 6.4%; P = .007); however, it increased grade ≥ 2 thrombocytopenia (16.2% vs 12.4%; P = .012). No significant difference was found in the incidence of adverse events between the groups.
Although the mechanisms of action underlying the effects of Jianpi Bushen have yet to be elucidated, our previous work showed that it prevented chemotherapy (CAPOX)-induced tissue damage by regulating apoptosis-related genes through PI3K/AKT and MAPK signaling pathways.10
Concluding Thoughts
This is the first rigorous randomized clinical trial of herbal medicine in patients with colon cancer receiving adjuvant treatment. Use of the traditional Chinese medicine formulation Jianpi Bushen appeared to lead to significant improvements in chemotherapy completion rates, particularly in those with stage II cancer and a younger age, by relieving chemotherapy-related adverse effects and improving quality of life. Future investigations are needed to evaluate the effects of Jianpi Bushen on long-term survival outcomes. The findings may help both patients and clinicians make evidence-based decisions about whether to use herbal medicine during cancer treatment.
As patients increasingly desire herbal products for symptom control, rigorous research is necessary to ensure their safety and its optimal use. Of note, the collaboration between ASCO and the Society for Integrative Oncology (SIO) has led to a concerted effort toward expanding clinical evidence for integrative therapies including herbal medicine.11
DISCLOSURE: Dr. Sun and Dr. Yang reported no conflicts of interest.
REFERENCES
1. Sung H, Ferlay J, Siegel RL, et al: Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71:209-249, 2021.
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5. Boyle JM, Kuryba A, Cowling TE, et al: Survival outcomes associated with completion of adjuvant oxaliplatin-based chemotherapy for stage III colon cancer: A national population-based study. Int J Cancer 150:335-346, 2022.
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7. Hassen G, Belete G, Carrera KG, et al: Clinical implications of herbal supplements in conventional medical practice: A US perspective. Cureus 14:e26893, 2022.
8. Pochet S, Lechon AS, Lescrainier C, et al: Herb-anticancer drug interactions in real life based on VigiBase, the WHO global database. Sci Rep 12:14178, 2022.
9. Sun L, Xu Y, Chen N, et al: Chinese herbal medicine (JianPi-BuShen) and completion rate of adjuvant chemotherapy for patients with stage II and III colon cancer: A randomized clinical trial. Eur J Cancer 213:115109, 2024.
10. Li G, Liu L, Yin Y, et al: Network pharmacology and experimental verification-based strategy to explore the underlying mechanism of Liu Jun An Wei formula in the treatment of gastrointestinal reactions caused by chemotherapy for colorectal cancer. Front Pharmacol 13:999115, 2022.
11. Gowin K, Muminovic M, Zick SM, et al: Integrative therapies in cancer care: An update on the guidelines. Am Soc Clin Oncol Educ Book 44:e431554, 2024.
Dr. Sun is Visiting Investigator, Integrative Medicine, Memorial Sloan Kettering Cancer Center, New York, and Associate Chief Physician in the Oncology Department at Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China. Dr. Yang is Academic Leader of the Oncology Department at Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
