World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access
Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc
Journal website https://wjon.elmerpub.com

Original Article

Volume 16, Number 6, December 2025, pages 609-620

Efficacy of Tegafur-Uracil Maintenance Therapy in Non-Metastatic Head and Neck Squamous Cell Carcinoma: A Meta-Analysis With Trial Sequential Analysis

Figures

↓  Figure 1. PRISMA flow diagram for study selection. PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
Figure 1.
↓  Figure 2. Forest plot for progression-free survival (PFS) in head and neck squamous cell carcinoma (HNSCC). HR: hazard ratio; CI: confidence interval.
Figure 2.
↓  Figure 3. Trial sequential analysis for progression-free survival (PFS-TSA). The blue line represents the cumulative Z-curve, which crosses both the conventional boundary for benefit (inner green line, Z = 1.96) and the trial sequential monitoring boundary for benefit (outer dashed red line). The cumulative sample size (1,280 patients) has reached 90.6% of the required information size (APIS = 1,413 patients, vertical red line), suggesting that the evidence for a benefit in PFS is sufficient and conclusive.
Figure 3.
↓  Figure 4. Forest plot for overall survival (OS) in head and neck squamous cell carcinoma (HNSCC). HR: hazard ratio; CI: confidence interval.
Figure 4.
↓  Figure 5. Trial sequential analysis for overall survival (OS-TSA). The blue line represents the cumulative Z-curve. Although the Z-curve has crossed the conventional boundary for benefit (inner green line, Z = 1.96), it has not yet crossed the more stringent trial sequential monitoring boundary (outer dashed red line). The cumulative sample size (1,373 patients) has only reached 75.6% of the required information size (APIS = 1,816 patients, vertical red line). This indicates that while there is a trend towards benefit, the evidence is not yet conclusive, and further studies are needed.
Figure 5.

Tables

↓  Table 1. Characteristics of Studies Evaluating UFT Maintenance Therapy in Advanced Head and Neck Cancers
 
Study (HNSCC) Cancer type Stage Prior treatment Treatment groups Sample size
UFT: tegafur-uracil; HNSCC: head and neck squamous cell carcinoma; CCRT: concurrent chemoradiotherapy; OC: oral cavity; OPx: oropharynx; HPx: hypopharynx; Lx: larynx.
Huang et al, 2021 [19] OC IVa and IVb Surgical resection and CCRT with cisplatin-based regimen UFT vs. non-UFT 93 (51 UFT, 42 non-UFT)
Huang et al, 2022 [20] OC IVa and IVb Curative surgical resection followed by adjuvant cisplatin-based CCRT UFT vs. non-UFT 103 (64 UFT, 39 non-UFT)
Lien et al, 2023 [21] HPx 25% III, 75% IVa-IVb Total laryngopharyngectomy followed by adjuvant CRT UFT vs. non-UFT in cortactin-positive and cortactin-negative patients 157 total (53 cortactin+, 104 cortactin-)
Yeh et al, 2021 [22] OC, OPx, HPx 21% III, 79% IVa-IVb Surgical resection, CCRT or chemotherapy UFT vs. non-UFT 240 (96 UFT, 144 non-UFT)
Hsieh et al, 2018 [9] OC 13% III, 87% IV Curative surgery and postoperative chemoradiotherapy UFT vs. non-UFT 356 (114 UFT, 242 non-UFT)
Hsieh et al, 2025 [23] OC, OPx, HPx, Lx 9% stage I-II, 91% stage III-IVB Definitive chemoradiotherapy without surgical intervention UFT vs. non-UFT 424 (212 UFT, 212 non-UFT)

 

↓  Table 2. Patient Demographics and Disease Characteristics in UFT Maintenance Therapy Studies
 
Study (HNSCC) Mean age (years) Gender (male %) ECOG PS (0 - 1) % T classification N classification
UFT: tegafur-uracil; HNSCC: head and neck squamous cell carcinoma; ECOG PS: Eastern Cooperative Oncology Group performance status.
Huang et al, 2021 [19] UFT: 51.61 UFT: 90.2% UFT: 92.0% T3-T4: UFT 72.55% N2-N3: UFT 60.78%, non-UFT 57.14%
Non-UFT: 57.10 Non-UFT: 88.1% Non-UFT: 66.66% Non-UFT 73.81%
Huang et al, 2022 [20] UFT: 49.8 ± 8.8 UFT: 90.6% 100% (all ECOG PS 1) T4: UFT 46.9% N3B: UFT 82.8%, non-UFT 92.3%
Non-UFT: 49.9 ± 11.5 Non-UFT: 92.3% Non-UFT 61.5%
Lien et al, 2023 [21] Median: 54 98% (both groups) Not reported pT3-4: cortactin+ 70%, cortactin- 65% pN3: cortactin+ 68%, cortactin- 51%
Yeh et al, 2021 [22] UFT: 56 ± 10 UFT: 97.9% Not reported Not reported Not reported
Non-UFT: 54 ± 10 Non-UFT: 97.2%
Hsieh et al, 2018 [9] UFT: 52 ± 10 UFT: 98% Not reported Not reported Not reported
Non-UFT: 54 ± 11 Non-UFT: 93%
Hsieh et al, 2025 [23] UFT: 42% > 60 years UFT: 95% Not reported T1-T2: UFT 39%, non-UFT 41%; N0-N1: UFT 37%, non-UFT 30%
Non-UFT: 36% > 60 years Non-UFT: 92% T3-T4: UFT 61%, non-UFT 59% N2-N3: UFT 63%, non-UFT 70%