Comparison of 24 Versus 46-Hour 5-FU Infusion Durations in the Perioperative FLOT Therapy for Gastric Cancer

Background and Objectives: This study aimed to evaluate the effects of 24 h versus 46 h continuous 5-fluorouracil (5-FU) infusion durations on pathological response, progression-free survival (PFS), and overall survival (OS) in patients with gastric and gastroesophageal junction adenocarcinoma receiving a perioperative FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) regimen. Materials and Methods: A total of 300 patients who received a perioperative FLOT regimen were retrospectively analyzed. The patients were divided into two groups as those receiving 24 h and 46 h continuous 5-FU infusion. Clinicopathological characteristics were compared. Survival analyses were evaluated using the Kaplan-Meier method. Factors affecting pathological response were analyzed by logistic regression, and factors affecting survival were examined by Cox regression analysis. Results: Pathological response rates were found to be significantly higher in patients receiving 46 h 5-FU infusion (multivariate analysis: OR = 2.884; 95% CI: 1.619-5.138; p < 0.001). The probability of pathological response was found to be significantly lower in patients with baseline cT4 and advanced nodal stage. Median OS times were 41.23 months and 33.73 months in the 24 h and 46 h groups, respectively, with no significant difference detected between the groups (p = 0.371). In contrast, median PFS time was significantly longer in the 24 h group (38.47 months vs. 18.00 months; p < 0.001). However, in multivariate analysis, 5-FU infusion duration could not be demonstrated as an independent prognostic factor for PFS. Moderately and poorly differentiated tumors and an increased number of positive lymph nodes were found to be independent risk factors for progression. Conclusions: Although 46 h 5-FU infusion in the perioperative FLOT regimen was associated with a higher pathological response rate, this advantage was not reflected in survival outcomes. It is considered that the observed difference in PFS may stem from the clinicopathological heterogeneity between the groups. Prospective randomized studies are needed to determine the optimal 5-FU infusion duration.