Efficacy of total neoadjuvant chemotherapy in the FLOT regimen in patients with locally advanced gastric and gastroesophageal junction: results of a phase II study

Background. The established approach notably improving the therapeutic outcomes for locally advanced gastric cancer and gastroesophageal junction cancer, presently entails the amalgamation of perioperative chemotherapy aligned with the FLOT protocol and surgical intervention. However, this approach harbors limitations, as only half of the patient cohort successfully completes the entire prescribed course of drug therapy. The potential solution to this problem lies in the complete transfer of the chemotherapy volume to the preoperative period and the execution of total neoadjuvant chemotherapy with FLOT regimen. Aim. Aim is to conduct a comparative assessment of the efficacy and safety between total neoadjuvant and perioperative chemotherapy with FLOT regimen for patients with locally advanced gastric cancer and gastroesophageal junction cancer. Materials and methods. In a retrospective study we enrolled patients with histologically confirmed locally advanced gastric cancer and gastroesophageal junction cancer meeting clinical stage criteria T2–4 and N0–3, without of distant metastases, treated between 2014 and 2020 at Federal State Budgetary Institution “N. N. Blokhin National Medical Research Center of Oncology” оf the Ministry of Health of the Russian Federation and Moscow City Oncologic Hospital No. 62 Department of Healthcare of Moscow. Participants in the control group underwent 8 courses of perioperative chemotherapy (4 preoperatively and 4 postoperatively), while those in the experimental group received 8 courses of total neoadjuvant chemotherapy. Both groups received drug therapy according to the FLOT protocol: 5-fluorouracil 2600 mg/m 2 , intravenous drip, over 24 hours, leucovorin 200 mg/m 2 , intravenous drip, oxaliplatin 85 mg/m 2 , intravenous drip, docetaxel 50 mg/m 2 , intravenous drip, on day 1, with a 14-day intercourse interval. The primary endpoint was one-year progression-free survival. Results. In the study included 187 patients. Participants were divided into two groups: 95 in the total neoadjuvant chemotherapy group and 92 in the perioperative chemotherapy group. The one-year progression-free survival was higher in the total neoadjuvant chemotherapy group at 79 %, compared to 68 % in the perioperative chemotherapy group (HR 0.54, 95 % confidence interval 0.32–0.9, p = 0.02). Median disease-free survival was 27.2 and 19.5 months in the neoadjuvant and perioperative chemotherapy groups, respectively. The tolerability of the entire planned drug treatment regimen was superior in the total neoadjuvant chemotherapy group, reaching 88.4 %, as opposed to 57.6 % in the perioperative chemotherapy group ( p = 0.0001). Conclusion. Among patients with locally advanced gastric cancer and gastroesophageal junction cancer, the application of total neoadjuvant chemotherapy according to the FLOT protocol, administered over 8 courses, demonstrated enhanced one-year progression-free survival and improved tolerability of the entire planned treatment regimen.