Lessons learned from the use of capecitabine-based triplet neoadjuvant chemotherapy in locally advanced esophageal...

Triplet neoadjuvant chemotherapy has demonstrated survival benefit in randomized trials for locally advanced esophageal squamous cell carcinoma (LA-ESCC); however, real-world delivery of infusional 5-fluorouracil-based regimens can be challenging in resource-constrained settings due to inpatient requirements, toxicity, and catheter-related complications. We describe our institutional experience with a capecitabine-based triplet neoadjuvant approach, focusing on feasibility, tolerability, and practical implementation rather than comparative efficacy. This single-centre retrospective review included treatment-naïve patients with LA-ESCC referred for neoadjuvant chemotherapy between April 2023 and October 2024. All patients received a capecitabine-based triplet regimen comprising a taxane, platinum, and metronomic oral capecitabine (650 mg/m2 twice daily). Clinical response, treatment delivery, pathological outcomes among resected patients, toxicity, and early survival were evaluated descriptively. Sixty-five consecutive patients were analysed. Neoadjuvant chemotherapy completion rates were high (95.9%), with most patients receiving planned cycles with limited dose modifications. Radiological tumour regression was frequently observed (objective response rate, 84.9%). Among patients deemed operable at baseline (n = 52), 34 (65.4%) proceeded to surgery. Among resected patients, major and complete pathological responses were observed in 58.8% and 41.2%, respectively. Treatment-related toxicities were common, with grade ≥ 3 adverse events occurring in 43.1% of patients, reflecting substantial treatment intensity but manageable within structured supportive care pathways. Median follow-up was short, and survival outcomes remain immature. This experience highlights practical considerations for delivering triplet neoadjuvant chemotherapy using an oral fluoropyrimidine backbone. While not intended to establish causal efficacy, these findings may inform centres considering similar approaches and support the need for prospective evaluation.