Non-fluorouracil/cisplatin versus fluorouracil/cisplatin regimens in chemoradiation for esophageal cancer: a systematic review and meta-analysis
Year: 2026
Type: article
Study designs: Systematic Review, Meta-Analysis
Abstract: Background: Definitive concurrent chemoradiation (CCRT) is the standard treatment for unresectable locally advanced esophageal cancer (EC), with 5-fluorouracil and cisplatin (FP) as the conventional concurrent chemotherapy backbone. However, the comparative efficacy and toxicity of non-FP regimens remain unclear. Therefore, this systematic review and meta-analysis aimed to compare the efficacy and toxicity of non-FP regimens versus the standard FP regimen in definitive CCRT for locally advanced unresectable EC. Methods: We conducted a systematic review and meta-analysis following PRISMA guidelines. PubMed, EMBASE, and the Cochrane Library were searched up to July 2026 for randomized controlled trials (RCTs) and retrospective studies comparing at least two CCRT regimens. Meta-analysis was performed for RCTs directly comparing FP versus non-FP regimens; other comparisons were summarized narratively. Risk of bias was assessed using Cochrane RoB 2.0 for RCTs and the Newcastle-Ottawa Scale for observational studies. Results: =0%]. Objective response rates (ORRs) and progression-free survival (PFS) varied substantially across studies. Grade ≥3 hematological toxicity differed significantly between specific regimens in six studies. Notably, 10 of 13 studies exclusively enrolled squamous cell carcinoma patients, and radiotherapy techniques/doses varied widely [intensity-modulated radiotherapy (IMRT) in 6 studies, three-dimensional conformal radiotherapy (3D-CRT) in 7; total doses 50-70 Gy], which complicates the attribution of non-hematological toxicities to chemotherapy alone. Conclusions: Pooled RCT evidence does not demonstrate an OS benefit of non-FP over FP in definitive CCRT for locally advanced EC. Given the predominance of squamous cell carcinoma and the heterogeneity in radiotherapy delivery, our findings are most applicable to this histology. Toxicity profiles vary, suggesting that patient tolerability should be a key consideration in regimen selection.
Source: Translational Cancer Research
Authors: Ming Chen, JunTao Ran, Fan Ding, Mingjun Zhao
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7224110485