Huachansu combined with chemotherapy for advanced gastrointestinal malignancies: a systematic review and meta-analysis with formulation-stratified analyses

Aim To evaluate the clinical effects of Huachansu combined plus chemotherapy compared with chemotherapy alone in advanced gastrointestinal malignancies and to explore potential variation in treatment-effect estimates across Huachansu formulations. Methods PubMed, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang database, Chinese Science and Technology Journal Database (VIP), and SinoMed (CBM) were searched from inception to 27 May 2026. Randomized controlled trials (RCTs) comparing Huachansu plus chemotherapy with chemotherapy alone were included. Forty-three RCTs involving 3,255 participants and three Huachansu formulations (injection, capsule, and tablet) were eligible. Primary outcomes were disease control rate (DCR) and objective response rate (ORR). Secondary outcomes included overall survival (OS), 3-year survival rate, quality of life, tumor markers, immune indices, angiogenic factors, and reported treatment-related adverse events. Results Compared to chemotherapy alone, Huachansu combined with chemotherapy was associated with higher DCR (RR = 1.20, 95% CI: 1.16–1.24) and ORR (RR = 1.42, 95% CI: 1.33–1.51). Formulation-stratified analyses identified a significant subgroup difference for DCR (χ 2 = 10.25, P = 0.006), but not for ORR (χ 2 = 4.75, P = 0.09). Survival data suggested a potential association with longer overall survival (MD = 2.02 months, 95% CI: 1.42 to 2.63; 2 RCTs) and a higher 3-year survival rate (RR = 1.96, 95% CI: 1.20 to 3.20; 3 RCTs). Tumor-biomarker analyses suggested associations with lower CEA (SMD = −1.59, 95% CI: −2.05 to −1.12; I 2 = 91%), CA19-9 (SMD = −1.35, 95% CI: −1.78 to −0.92; I 2 = 89%), and CA125 (SMD = −1.16, 95% CI: −1.47 to −0.84; I 2 = 64%). Favorable changes were also reported in quality-of-life and selected immune- and angiogenesis-related outcomes. Lower reported incidences of gastrointestinal reactions, oral mucositis, peripheral neuropathy, leukopenia, thrombocytopenia, and hepatic/renal injury were observed. Conclusion Huachansu plus chemotherapy may provide additional clinical benefits in advanced gastrointestinal malignancies, with higher short-term tumor response rates, greater improvements in quality of life, and lower adverse events. Changes in tumor, immune, and angiogenesis-related biomarkers offer exploratory biological insights. Formulation-stratified findings remain inconclusive because of indirect comparisons, and further high-quality, adequately powered RCTs are warranted. Systematic Review Registration PROSPERO identifier CRD420261406854.