A Chinese herb formula, Qu-yu-jie-du decoction, improves postoperative survival in metastatic colorectal cancer

Introduction

In recent years, advances in surgical techniques and systemic therapies have enabled a subset of metastatic colorectal cancer (mCRC) patients to attain no evidence of disease (NED) status following complete tumor resection or localized treatment. However, this does not guarantee eradication: approximately 60–70 % of these patients (as reported in the JCOG0603 and EORTC40983 studies) experience recurrence or metastasis within five years—a leading cause of mortality.

Although adjuvant chemotherapy can extend postoperative disease-free survival (DFS)—improving rates from 38.7 % to 49.8 % in JCOG0603—it does not significantly improve overall survival (OS). In unresectable or partially resected mCRC, maintenance regimens such as capecitabine monotherapy after induction chemotherapy or bevacizumab plus capecitabine (e.g., the CAIRO3 trial) yield only modest progression-free survival gains and are not indicated for patients rendered disease-free by surgery. Attempts to prolong adjuvant chemotherapy beyond six months (e.g., the IDEA collaboration) likewise do not improve survival and increase cumulative toxicities (e.g., neuropathy, myelosuppression). Moreover, some studies suggest that postoperative chemotherapy may induce resistance in dormant tumor cells, ultimately shortening OS after recurrence.

QYJD decoction is a traditional Chinese medicine (TCM) formula composed of eight herbal ingredients (Table 1A), including Persicae Semen (Taoren) and Eupolyphaga seu Steleophaga (Tubie), and is traditionally used in colorectal cancer treatment.

Previous studies have shown that QYJD decoction inhibits colon cancer stem cell proliferation and migration (HCT116) (Tian-Tian et al., 2020), and provides protective effects in animal models by activating the Nrf2 antioxidant pathway and reducing inflammation (Fang et al., 2018). It has also been found to decrease myeloperoxidase (MPO) activity and reduce pro-inflammatory cytokines such as IL-1β, IL-6, TNF-α, and chemokines like CCL2 and CXCL2 in colon tissues (Zhao et al., 2022). Additionally, QYJD decoction mitigates macrophage infiltration and liver metastatic tumor volumes by regulating the CCL2/CCR2 signaling axis and modulating epithelial-mesenchymal transition (Zhao et al., 2022). From a TCM perspective, postoperative colorectal cancer patients transition from a state of 'excess' to 'deficiency' due to the effects of surgery and chemotherapy, often leading to a recurrence of 'stasis-toxicity' as the disease progresses. This imbalance, marked by residual 'hidden toxins' and blood stasis, is central to the disease's pathogenesis. TCM interventions aim to resolve this imbalance by clearing 'phlegm,' eliminating 'stasis,' and addressing 'dampness.' Preliminary evidence suggests that QYJD decoction not only addresses these imbalances but also modulates the inflammatory microenvironment by regulating M2 macrophage-related inflammatory factors such as IL-1β, IL-6, TGF-β, and CCL2, which aligns with the inflammatory-lactate signaling pathway. This pathway has been implicated in tumor progression and metastasis, supporting the hypothesis that QYJD decoction may prevent postoperative recurrence and metastasis by targeting chronic inflammation and metabolic disturbances in the tumor microenvironment.

Purpose: To determine whether QYJD decoction improves disease-free survival (DFS) and modulates inflammation/lactate metabolism in postoperative mCRC-NED patients.

Methods/design: In this single-center randomized trial, 140 stage IV mCRC patients achieving post-resection NED status were randomized at a ratio of 1:1 to either a QYJD group (200 mL/day for 2 years) or a control group (routine follow-up). Two patients per group withdrew consent prior to the intervention, resulting in an intention-to-treat (ITT) population of 136 patients (68 per group) for the final analysis. All received standard adjuvant chemotherapy. The primary outcome was DFS; secondary outcomes were OS, 1-/2-/3-year survival rates, adverse events, and inflammation/lactate metabolism markers.

Results: Compared to the control group, QYJD decoction significantly improved DFS throughout the observation period (HR = 0.515, p = 0.004). The 1-year DFS rate was 91.2 % (62/68) in the QYJD group versus 73.5 % (50/68) in the control group (p < 0.01); the 2-year DFS rate was 56.9 % (40/68) in the QYJD group versus 35.1 % (25/68) in the control group (p = 0.002); and the 3-year DFS rate was 47.4 % (32/68) in the QYJD group versus 32.4 % (22/68) in the control group (p = 0.03). Significant differences were observed across all time points (1-year, 2-year, and 3-year) for DFS. Regarding overall survival (OS), the 2-year OS rate was 95.4 % (65/68) in the QYJD group versus 85.1 % (58/68) in the control group (p = 0.01), and the 3-year OS rate was 68.7 % (47/68) in the QYJD group versus 57.7 % (39/68) in the control group (HR = 0.407, p = 0.019). QYJD also significantly reduced inflammatory markers and lactate dehydrogenase (LDH) (p < 0.05). The most common adverse events were grade 1 hematologic toxicity, anorexia, diarrhea, and nausea, which were generally mild and manageable.

Conclusion: QYJD decoction significantly improves DFS and shows OS benefits in postoperative mCRC-NED patients. It also reduces systemic inflammation/LDH, and in terms of safety, only causes mild adverse events.

Reference:

Jiaming Wu , Cui Shao , Yu Dong , Jincheng Meng , Huatang Zhang , Liming Lu , Lizhu Lin , Cantu Fang . Qu-yu-jie-du decoction maintenance therapy improves postoperative survival in metastatic colorectal cancer: a single-center randomized trial with 36-month follow-up. Phytomedicine. 2025 Oct:146:157143. doi: 10.1016/j.phymed.2025.157143.