5-Fu-Based Doublet Regimen in Patients Receiving Perioperative or Postoperative Chemotherapy for Locally Advanced Gastric Cancer: When to Start and How Long Should the Regimen Last?

Background The duration and the optimal time to adjuvant chemotherapy (TAC) in locally advanced gastric cancer (LAGC) have net not been sufficiently demonstrated. Sequential adjuvant chemotherapy (AC) after neoadjuvant chemotherapy plus gastrectomy is increasingly utilized, making the question more complicated. Patients and Methods Data were collected from patients with LAGC who underwent 5-Fu-based doublet regimens as adjuvant treatment after gastrectomy in a single-center database. TAC and duration (cycles) were used to evaluate survival outcomes. Results A total of 816 patients were included. Patients received over six cycles and TAC less than 42 days significantly correlated with better survival (log-rank Ptrend<0.001). The analysis of TAC and number cycles were separately applied in perioperative chemotherapy (PEC) and postoperative chemotherapy (POC) group using Cox regression. The number of cycles revealed a statistical significance improving OS rate both in POC (HR=0.904, 95% CI=0.836-0.977, P=0.011) and PEC (HR=0.887, 95% CI=0.798-0.986, P=0.026), while only in POC did the TAC show an increasing trend of risk with borderline significance (OS: HR=1.008, 95% CI=0.999-1.018, P=0.094; PFS: HR=1.009, 95% CI=1.000-1.018, P=0.055). A spline model demonstrates the less improvement in survival after cycles of chemotherapy reaching six. Conclusion Our findings suggest that TAC is more likely to downregulate the survival benefit in POC rather than PEC, while overall survival is susceptible to cumulative cycles of chemotherapy in both groups. Furthermore, six cycles of chemotherapy tended to reach the maximum survival benefits. Prospective confirmation is required.