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Purpose. To study the efficacy and safety of total neoadjuvant chemotherapy (NACT) with the FOLFIRINOX regimen for locally advanced gastric (GC) and cardioesophageal junction (CEJ) cancer.Patients and methods. Patients with histologically confirmed locally advanced gastric adenocarcinoma and CEJ, clinical stage cT3 or higher and/or regional lymph node involvement (cN+), without evidence of distant metastasis were included in our open-label, single-centre, non-randomised study. In the FLOT control group, patients received 4 courses preoperatively and 4 postoperatively with follow-up. I In the FOLFIRINOX group 8 courses of chemotherapy were administered in neoadjuvant mode, followed by surgery and observation. The tumor regression grade was assessed in accordance with Becker, Mandard and G. A. Lavnikova scales.Results. The study included 136 patients, 119 of whom started treatment according to the protocol (ITT population). Fiſty-nine patients were enrolled into the FLOT group and 60 into the FOLFIRINOX group. One-year progression-free survival (PFS) was 67,5 % in the FLOT group and 90,4 % in the FOLFIRINOX group (p = 0,29). The estimated 2-year PFS in the FLOT group was 61,4 % [95 % CI, 48,4–77,9 %]. Median PFS and overall survival (OS) were not reached. The incidence of events (progression or death) was lower in the FOLFIRINOX group (odds ratio [OR] 0,40 [95 % CI 0,16–0,97, p = 0,047]). Adverse prognostic factors regardless of treatment were lymphatic (L1), vascular (V1) and perineural invasion (Pn1), and regional lymph node involvement aſter chemotherapy (ypN+) [p = 0,046; p = 0,014; p = 0,0021; p = 0,04, respectively]. There was no correlation between pathological complete response and survival rates.Conclusion. Total neoadjuvant chemotherapy with the FOLFIRINOX regimen for locally advanced GC/ CEJ demonstrated comparable to the perioperative FLOT one-year PFS rate. No association was found between tumor regression grade and survival outcomes.

Gastric cancer (GC) is the fifth most common malignant neoplasm in the world among all malignant tumors. Currently, the “gold” standard of treatment for patients with non‑metastatic cancer of the stomach and esophageal–gastric junction is surgical treatment, which is complemented by perioperative chemotherapy according to the FLOT scheme, which includes four courses of therapy before surgery and four after. However, according to statistics, less than half of patients complete all adjuvant courses of FLOT chemotherapy due to the high toxicity of the regimen and a decrease in the functional status of patients in the postoperative period. In this regard, studies are being conducted to study the tolerability of total neoadjuvant chemotherapy, when all courses are held at the preoperative stage in order to carry out all stages of treatment in full. International studies have shown the results of the use of targeted (ramucirumab, trastuzumab, pertuzumab), immune drugs (pembrolizumab, nivolumab, ipilimumab), S‑1 in combination with chemotherapy as part of the combined treatment of gastric and esophageal‑ gastric junction cancer. The emergence of new therapeutic agents previously studied in metastatic GC may change approaches to the treatment of localized and locally advanced GC.The review presents the features of perioperative therapy regimens in patients with resectable gastric and esophageal‑ gastric junction cancer in order to reduce the frequency of local and long‑term relapses and improve further prognosis.