Objective  To compare the efficacy and safety of perioperative chemotherapy regimens based on docetaxel administered in different cycles for locally advanced gastric cancer (LAGC) and gastroesophageal junction cancer (GEJC) through a network Meta-analysis.

Methods  PubMed, Embase, Cochrane Library, and Web of Science databases were electronically searched to collect randomized controlled trials (RCTs) evaluating docetaxel-based perioperative regimens for the treatment of LAGC and GEJC from inception to February 28, 2025. Two researchers independently screened the literature, extracted relevant data, and assessed the risk of bias in the included studies. Subsequently, a network Meta-analysis was performed using R 4.5.0 software.

Results  A total of 10 RCTs involving 2,064 patients were included. The results of the network Meta-analysis showed that, compared with three cycles of epirubicin, cyclophosphamide, and fluorouracil (ECF regimen) and four cycles of platinum and fluorouracil (PF regimen), both three-cycle and four-cycle docetaxel, platinum, and fluorouracil (TPF regimen) significantly increased the complete tumor resection rate (R0 resection rate). Compared with surgery alone, the three-cycle TPF regimen significantly improved the R0 resection rate. Additionally, the four-cycle TPF regimen significantly improved 3-year and 5-year progression-free survival (PFS) compared with the two-cycle PF regimen, and significantly improved overall survival (OS) at 3 and 5 years compared with the three-cycle ECF regimen. Compared with surgery alone, the three-cycle TPF regimen also significantly increased the pathological complete response rate (pCR rate). Furthermore, compared with the two-cycle TPF and three-cycle ECF regimens, the four-cycle TPF and PF regimens were associated with a lower risk of surgical complications. Conversely, the two-cycle TPF and three-cycle ECF regimens significantly increased the risk of surgical complications compared with surgery alone. No statistically significant differences were observed in the incidence of grade 3 to 4 adverse events among the treatment regimens (P>0.05). Based on the surface under the cumulative ranking curve (SUCRA) plot and pairwise comparisons, the three-cycle PF regimen appeared to be the most effective in achieving the highest R0 resection rate, the three-cycle TPF regimen appeared to be the most effective in achieving the highest pCR rate, while the four-cycle TPF regimen was associated with the best outcomes in terms of 3-year and 5-year PFS and OS.

Conclusion  The four-cycle TPF regimen may be associated with the optimal PFS and OS among perioperative chemotherapy regimens. No statistically significant differences were observed between the four-cycle TPF and the three-cycle PF in terms of R0 resection rate, between the four-cycle TPF and the three-cycle TPF in terms of pCR rate, or between the four-cycle TPF and the other seven regimens included in the study in terms of safety assessment. The four-cycle TPF regimen may represent the optimal perioperative chemotherapy regimen for patients with LAGC and GEJC.

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