Treatment discontinuation associated with perioperative toxicity of FLOT versus XELOX chemotherapy in patients with resectable gastric cancer: prospective randomized trial (PECORINO).

Background: Gastric cancer represents a significant global health burden, necessitating effective multimodal treatment approaches. Neoadjuvant chemotherapy has gained prominence in improving outcomes, with FLOT (5-fluorouracil, leucovorin, oxaliplatin and docetaxel) and XELOX (capecitabine and oxaliplatin) emerging as potential regimens. This study aims to compare the efficacy and safety of neoadjuvant FLOT and XELOX in resectable gastric cancer. Methods: We conducted a prospective randomized open-label clinical trial. Sixty-nine patients with resectable gastric cancer were randomly assigned to perioperative 8 cycles of FLOT and 8 cycles of XELOX and curative surgery. The primary endpoint was the proportion of patients who fully adhered to all the allocated treatment per protocol. Secondary endpoints were pathological regression grade, progression-free survival, overall survival, chemotherapy and surgery complications rates. Results: A total of 69 patients were included in both arms. Thirty-three of 35 (94.3%) patients in the FLOT arm and 23 of 34 (67.6%) in the XELOX arm underwent curative-intent surgery after neoadjuvant treatment. Nineteen (54.3%) and 17 (50%) patients completed the protocol-defined therapy in the FLOT and XELOX arms, respectively (P=0.81). The proportion alive without progression at 2 years was 18.8% [95% confidence interval (CI): 8.9-39.8%] in the XELOX group compared to 45.7% (95% CI: 31.9-65.6%) in the FLOT group. The study was prematurely terminated due to the inferiority of the XELOX regimen in preoperative settings because of the high rate of disease progression. Conclusions: In our study, the rate of protocol completion did not statistically differ between the two groups. Perioperative FLOT chemotherapy exhibits notable efficacy in gastric cancer management, as evidenced by favorable treatment responses and surgical outcomes. The regimen's safety profile aligns with established expectations. This study supports the continued exploration of FLOT as a valuable component in the perioperative care of gastric cancer patients. Trial Registration: ClinicalTrials.gov ID NCT04937738.