Efficacy and safety of thymosin α1 combined with chemotherapy for gastric cancer: a systematic review and meta-analysis of randomized controlled trials

Objective To systematically evaluate the efficacy and safety of thymosin α1 combined with chemotherapy in the treatment of gastric cancer. Methods A systematic search of 8 electronic databases was conducted to identify relevant RCTs. Meta-analysis was performed using Stata 18.0. Meta-regression, subgroup analyses, sensitivity analyses, and publication bias analyses were conducted to further examine results, and reliability of findings was assessed using TSA and GRADE. Results 20 RCTs involving 1,704 patients were included. Meta-analysis results showed that, thymosin α1 combined with chemotherapy was associated with higher ORR (RR = 1.39), DCR (RR = 1.16), and KPS scores (WMD = 8.27). Regarding immune function, combination therapy resulted in higher CD3 + % (WMD = 7.73), CD4 + % (WMD = 6.87), CD4 + /CD8 + (WMD = 0.42), and NK cell (WMD = 4.73). Regarding tumor markers, combination therapy resulted in lower levels of CEA (WMD = −5.48) and CA199 (WMD = −9.06). Regarding inflammatory factors, combination therapy may reduce levels of MMP-2, MMP-9, IL-4, and IL-10, while increasing levels of IFN-γ and TNF-α. Regarding safety, combination therapy was associated with reductions in gastrointestinal reactions (RR = 0.63), myelosuppression (RR = 0.60), abnormal liver function (RR = 0.54), and neurotoxicity (RR = 0.47). However, included RCTs did not systematically report long-term survival outcomes, and their methodological quality was limited; and GRADE indicated that quality of evidence for outcomes ranged from very low to moderate. Conclusion The combination of thymosin α1 with chemotherapy is associated with improved short-term efficacy, enhanced immune function, improved quality of life, and a reduced incidence of adverse reactions in patients with gastric cancer, indicating good potential for clinical application. However, it remains unclear whether this approach can provide long-term benefits for patients with gastric cancer. Furthermore, given that studies included were all small-sample studies conducted in China and were of limited quality, certainty of evidence is low; these conclusions require further validation through additional high-quality studies. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/ , Identifier CRD420261282679.