Modified FLOT chemotherapy shows acceptable delivery, manageable toxicity, and favorable survival in gastric/GEJ adenocarcinoma

Perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) is the established standard for resectable gastric and gastroesophageal junction (GEJ) adenocarcinoma. However, the standard FLOT regimen, particularly its high-dose fluorouracil component, often leads to significant toxicity, limiting treatment completion in routine practice. This can compromise patient outcomes and quality of life. Dose-modified FLOT regimens are frequently employed to enhance tolerability, yet robust data supporting their clinical efficacy and safety in real-world settings have been scarce, creating a critical gap in optimizing treatment delivery for these aggressive cancers.

This retrospective cohort study evaluated a predefined, modified perioperative FLOT regimen in 29 patients with resectable gastric or GEJ adenocarcinoma across three institutions between 2019 and 2025. The modified regimen consisted of fluorouracil 2,400 mg/m2 administered over 46-48 hours, oxaliplatin 85 mg/m2, and docetaxel 40-50 mg/m2. Researchers assessed safety (toxicity), treatment delivery, and key clinical outcomes, including overall survival (OS) and recurrence-free survival (RFS). Survival estimates were calculated using Kaplan-Meier methods, providing a real-world perspective on the regimen's performance.

Curative-intent resection was successfully achieved in 86% of patients, with an impressive R0 resection rate (no residual tumor at margins) of 88%. A pathological complete response (pCR) rate, indicating no viable tumor cells in the resected specimen, was observed in 16% of patients. At a median follow-up of 30.3 months, the median overall survival (OS) was 53.6 months, with a 3-year OS rate of 75.3%. Median recurrence-free survival (RFS) was 46.1 months, corresponding to a 3-year RFS rate of 52.4%. > The safety profile demonstrated manageable toxicity, with Grade 3 or higher neutropenia occurring in 34% of patients and infections in 10%, notably without any treatment-related deaths. These outcomes suggest that the dose-modified FLOT regimen maintains substantial efficacy while improving tolerability, supporting its feasibility in routine clinical settings.