Efficacy and safety of TiaoPi AnChang decoction to reduce CAPOX-Induced adverse reactions in Chinese patients with colorectal cancer: a randomized, double-blind, placebo-controlled trial

Purpose This study evaluated the efficacy of TiaoPi AnChang Decoction (TPACD) against CAPOX-induced adverse reactions (CIARs) and improving survival outcomes in colorectal cancer (CRC) patients receiving CAPOX as adjuvant chemotherapy. This paper presents an interim analysis of the clinical trial, with a primary focus on CIARs. Patients and methods This was a randomized, double-blind, placebo-controlled trial enrolling high-risk stage II or III CRC patients undergoing CAPOX who were diagnosed with spleen-kidney deficiency syndrome. The study planned to randomly assign 98 patients in a 1:1 ratio to either the TPACD group (30 mL orally, twice daily) or the placebo group (matched placebo). The trial duration spanned 4 chemotherapy cycles (approximately 84 days), during which we assessed the incidence of CIARs (graded via CTCAE), Traditional Chinese Medicine (TCM) syndrome scores, quality of life (QoL, evaluated via EORTC QLQ-C30), peripheral blood immune cell subsets, tumor markers, safety, and survival outcomes. A linear mixed-effects model was applied to adjust for baseline differences. Results Among 496 screened CRC patients, 108 were randomized into the TPACD group (n = 54) or the placebo group (n = 54). The incidence of overall CIARs was significantly lower in the TPACD group ( P = 0.009), particularly for grade ≥2 CIARs (37.77% vs. 67.70%, P = 0.008). Subgroup analyses revealed that the treatment effect was homogeneous, with no significant interaction observed between the treatment and the variables of age, sex, BMI, tumor size, or TNM stage (all P for interaction 0.05). TPACD administration resulted in improvements in symptoms including fatigue, nausea, vomiting, loss of appetite, and oxaliplatin-induced peripheral neuropathy. However, its efficacy in alleviating myelosuppression, hand-foot syndrome, and pain was limited. Additionally, TPACD improved overall QoL (least squares mean difference (LSMD) −11.71, P 0.001), attenuated the progression of spleen-kidney deficiency syndrome (LSMD 3.09, P 0.001), and positively influenced the CD4+/CD8+ ratio (1.91 ± 0.94 vs. 2.64 ± 1.04, P = 0.002). No additional hepatic or renal injury was observed. The predefined endpoints for survival outcomes had not been reached at the time of this analysis. Conclusion TPACD serves as an effective, safe, well-tolerated, and readily acceptable complementary therapy for CRC patients undergoing CAPOX. Clinical Trial Registration https://www.chictr.org.cn/index.html , identifier ChiCTR2200065759.