Phase II study of neoadjuvant chemotherapy with fluorouracil, leucovorin, oxaliplatin and docetaxel for resectable esophageal squamous cell carcinoma: Survival analysis.

350 Background: Based on the JCOG1109 trial, the combination of neoadjuvant docetaxel, cisplatin, and fluorouracil (DCF) followed by esophagectomy has become the standard of care for resectable locally advanced esophageal squamous cell carcinoma (ESCC). While the efficacy of DCF is promising, its toxicity raises concerns about its feasibility. Although the combination of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) demonstrated benefits for esophageal adenocarcinoma as a perioperative therapy, its safety and efficacy for patients with locally advanced ESCC have not been evaluated. Previously, neoadjuvant FLOT therapy showed a promising pathological response with acceptable toxicities based on the results from our multicenter phase II study. Here, we report survival outcomes in this population. Methods: We conducted a multicenter phase II study of neoadjuvant chemotherapy with FLOT for ESCC. Patients with cT1N1-3M0-1 or cT2-3N0-3M0-1 (only supraclavicular lymph node (SCLN) metastasis is included as M1) based on the 8th edition of the UICC TNM staging system were eligible. Neoadjuvant chemotherapy consisted of oxaliplatin (85 mg/m 2 ), docetaxel (50 mg/m 2 ), and l-leucovorin (200 mg/m 2 ) on day 1, followed by continuous infusion of fluorouracil (2600 mg/m 2 /day) for 24 hours. This regimen was repeated every two weeks with a maximum of four cycles. The prophylactic antibiotics and G-SCF were not used mandatory. Following completion of the neoadjuvant chemotherapy, esophagectomy with extended lymphadenectomy was performed. Adjuvant treatment was prohibited for all patients. The primary endpoint was the pathological response rate. Secondary endpoints included overall survival (OS) and progression free survival (PFS). The maximum expected number of patients to be enrolled was 60, with enrollment to be stopped when 45 patients with negative SCLN were enrolled. Results: Fifty-four eligible patients were enrolled between September 2020 and January 2024. The number of patients with cStage I/II/III/IVB were 3/16/27/8, respectively. Of 54 patients, 45 patients were M0 without SCLN metastasis. Excluding one patient who did not receive any treatment after enrollment, 53 patients were included in the full analysis set. The median follow up period was 27 months. Two-year OS rate in all patients (n=53) and in those without SCLN metastasis (n=44) was 78.2% and 76.4%, respectively. Two-year PFS rate in all patients and in those without SCLN metastasis was 50.4% and 49.4%, respectively. Conclusions: After follow up, neoadjuvant FLOT therapy demonstrated acceptable OS and PFS. This regimen may be considered as a treatment option for resectable locally advanced ESCC. Clinical trial information: jRCTs031200094 .