Non-fluorouracil/cisplatin versus fluorouracil/cisplatin regimens in chemoradiation for esophageal cancer: a systematic review and meta-analysis.
- 1Department of Nuclear Medicine, The First Hospital of Lanzhou University, Lanzhou, China.
- 2Department of Interventional Radiology, The First Hospital of Lanzhou University, Lanzhou, China.
- 3Teaching Experiment and Training Center, Gansu University of Chinese Medicine, Lanzhou, China.
Abstract
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. 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. Thirteen studies (9 RCTs, 4 retrospective; N=2,041) were included. Meta-analysis of four RCTs (n=955) showed no significant overall survival (OS) difference between non-FP and FP regimens [hazard ratio (HR) =0.94, 95% confidence interval (CI): 0.78-1.13; I2=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. 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.
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BibTeX
@article{chen2026nonfluorouracilcisplatin,
title = {{Non-fluorouracil/cisplatin versus fluorouracil/cisplatin regimens in chemoradiation for esophageal cancer: a systematic review and meta-analysis.}},
author = {Ming Chen and JunTao Ran and Fan Ding and Mingjun Zhao},
journal = {Translational cancer research},
year = {2026},
month = sep,
doi = {10.21037/tcr-2026-2030},
url = {https://europepmc.org/article/MED/42997714},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Non-fluorouracil/cisplatin versus fluorouracil/cisplatin regimens in chemoradiation for esophageal cancer: a systematic review and meta-analysis.
AU - Ming Chen
AU - JunTao Ran
AU - Fan Ding
AU - Mingjun Zhao
PY - 2026
DA - 2026/09/28
JO - Translational cancer research
DO - 10.21037/tcr-2026-2030
UR - https://europepmc.org/article/MED/42997714
AB - 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. 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. Thirteen studies (9 RCTs, 4 retrospective; N=2,041) were included. Meta-analysis of four RCTs (n=955) showed no significant overall survival (OS) difference between non-FP and FP regimens [hazard ratio (HR) =0.94, 95% confidence interval (CI): 0.78-1.13; I2=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. 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.
SN - 2218-676X
SN - 2219-6803
ER -