Safety and feasibility of total neoadjuvant FLOT chemotherapy in locally‑advanced gastric and gastroesophageal junction cancer

Gastric cancer is one of the leading causes of cancer-related mortality worldwide. While perioperative chemotherapy with the fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) regimen improves survival in resectable gastric and gastroesophageal junction (GEJ) cancer, postoperative treatment is frequently poorly tolerated. Total neoadjuvant chemotherapy (TNT), in which all chemotherapy is delivered prior to surgery, has emerged as a promising alternative. The present study aimed to investigate the safety and feasibility of TNT with FLOT in patients with resectable gastric and GEJ cancer. The study retrospectively analyzed patients who received TNT with FLOT followed by curative surgery at the National Cancer Institute in Kyiv (Ukraine), between October 2017 and October 2021. Primary endpoints included safety and feasibility, assessed by chemotherapy-related adverse events, dose reductions, treatment discontinuation and completion rate. Secondary endpoints included pathological response, R0 resection rate, postoperative morbidity and mortality, and surgical outcomes. A total of 76 patients were included in the study. Of these, 71 patients proceeded to curative-intent surgery after the neoadjuvant stage. Among all included patients, 42 (55.26%) patients completed all eight FLOT cycles, 14 (18.42%) patients completed seven cycles, 10 (13.16%) patients completed six cycles and 5 (6.58%) patients completed five cycles. Common toxicities included leukopenia (76.32% grade 1-2; 21.05% grade 3-4) and nausea (76.32% grade 1-2; 10.53% grade 3-4). An R0 resection was achieved in 66 patients (92.96%) and a complete pathological response in 2 patients (2.82%). In conclusion, TNT with FLOT is a safe and feasible option for resectable gastric and GEJ cancer. It is not associated with an increased rate of severe adverse events and mortality. However, the findings of the present study are not conclusive and further prospective studies should assess its long-term efficacy and integration with targeted therapies.