Tegafur
| 證據等級: L5 | 預測適應症: 10 個 |
目錄
Tegafur: From Gastrointestinal Cancers to Colonic Neoplasm
One-Sentence Summary
Tegafur is a prodrug of 5-fluorouracil (5-FU), traditionally used as a component of fluoropyrimidine combination regimens (UFT, S-1) for gastrointestinal malignancies including gastric cancer. The TxGNN model predicts it may be effective for Colonic Neoplasm, with 30 clinical trials and 20 publications currently supporting this direction — though the evidence largely confirms an already-established use rather than a novel repurposing signal.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Gastrointestinal cancers (e.g. gastric cancer), as prodrug component of UFT (tegafur+uracil) and S-1 (tegafur+gimeracil+oteracil) — no formal Germany/Taiwan license record available |
| Predicted New Indication | Colonic Neoplasm |
| TxGNN Prediction Score | 99.90% |
| Evidence Level | L1 |
| Germany Market Status | ✗ Not Marketed |
| Number of Authorizations | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Currently, a formal MOA record is not available in the drug-level field, but the evidence pack's mechanistic rationale is clear: tegafur is a prodrug of 5-fluorouracil, metabolically activated via hepatic CYP2A6. Once converted to 5-FU, it inhibits thymidylate synthase, blocking DNA synthesis — a classical antimetabolite chemotherapy mechanism.
Tegafur is never used alone clinically; it is formulated into combination products — UFT (tegafur + uracil, where uracil blocks 5-FU catabolism via DPD) and S-1 (tegafur + gimeracil + oteracil, adding DPD inhibition and gastrointestinal toxicity reduction). Both combinations are already established standard adjuvant/palliative chemotherapy regimens for colorectal cancer in multiple countries (notably Japan), as reflected by the very large body of Phase 3 trials below.
This means the TxGNN prediction is not identifying a truly novel indication, but rather recovering an already-approved use — the mechanism (antimetabolite disruption of DNA synthesis in rapidly dividing epithelial cells) is directly applicable to colonic adenocarcinoma, and the clinical evidence base is mature rather than exploratory.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00378716 | Phase 3 | Completed | 1608 | UFT+LV vs 5-FU+LV in resected stage II/III colon cancer |
| NCT00392899 | Phase 3 | Completed | 2025 | Adjuvant UFT vs observation in curatively resected stage II colon cancer |
| NCT00660894 | Phase 3 | Completed | 1535 | UFT+LV vs S-1 as adjuvant treatment for stage III colon cancer |
| NCT01918852 | Phase 3 | Completed | 161 | SALTO trial: S-1 vs capecitabine in first-line metastatic colorectal cancer |
| NCT00905047 | Phase 3 | Completed | 89 | Crossover comparison of capecitabine vs UFT+folinic acid in advanced/metastatic CRC |
| NCT00152230 | Phase 3 | Completed | 900 | NSAS-CC: postoperative UFT vs surgery alone in Dukes C colorectal cancer |
| NCT01225744 | Phase 2 | Completed | 47 | Cetuximab + irinotecan + oxaliplatin + UFT in first-line metastatic CRC |
| NCT00439517 | Phase 2 | Completed | 302 | FOLFOX-4+Cetuximab vs UFOX+Cetuximab in metastatic colorectal cancer |
| NCT00385970 | Phase 3 | Unknown | 380 | UFT+PSK vs UFT+LV as adjuvant therapy for stage IIB/III colorectal cancer |
| NCT02887365 | Phase 4 | Unknown | 300 | Tegafur-uracil as metronomic maintenance therapy in stage II MSI-L/MSS colon cancer |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 33714860 | 2021 | RCT | ESMO Open | ACTS-CC 02 5-year update: S-1+oxaliplatin not superior to UFT/LV in high-risk stage III colon cancer |
| 31917122 | 2020 | RCT | Clin Colorectal Cancer | ACTS-CC 02 phase III trial establishing UFT/LV as adjuvant comparator standard |
| 16648506 | 2006 | RCT | J Clin Oncol | NSABP C-06: oral UFT+LV vs IV 5-FU+LV in stage II/III colon carcinoma |
| 26347106 | 2015 | RCT | Ann Oncol | JFMC33-0502: optimal duration of UFT/LV adjuvant chemotherapy in stage IIB/III colon cancer |
| 15108041 | 2004 | RCT | Int J Clin Oncol | Adjuvant immunochemotherapy vs chemotherapy using UFT combinations in colorectal cancer |
| 6402917 | 1983 | RCT | Am J Clin Oncol | Oral tegafur vs IV 5-FU in metastatic colorectal cancer |
| 33950962 | 2021 | RCT/Cohort | Medicine | Taiwan NHIRD nationwide cohort: UFT vs 5-FU as postoperative adjuvant chemotherapy in stage II/III colon cancer |
| 35168560 | 2022 | Cohort | BMC Cancer | JFMC46-1201: UFT/LV efficacy in high-risk stage II colon cancer (propensity score matched) |
| 38833114 | 2024 | Cohort | Int J Clin Oncol | JFMC46-1201 final analysis: updated 5-year OS and risk factors |
| 25209093 | 2014 | Review | Clin Colorectal Cancer | Asian consensus guideline for metastatic colorectal cancer management |
Germany Market Information
No authorization records are available — tegafur (or its combination products UFT/S-1) is currently not marketed in Germany under this evidence pack (0 licenses on file).
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (Fluoropyrimidine class, 5-FU prodrug) |
| Myelosuppression Risk | Moderate — consistent with fluoropyrimidine class effects (neutropenia, thrombocytopenia); no drug-specific toxicity dataset provided |
| Emetogenicity Classification | Low to moderate |
| Monitoring Items | CBC with differential, liver and renal function; DPD/DPYD genotype screening recommended prior to initiation (per fluoropyrimidine safety evidence, e.g. NCT05266300) |
| Handling Protection | Must follow standard cytotoxic drug handling and disposal regulations |
Safety Considerations
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Multiple completed Phase 3 RCTs (n up to 2025) consistently support tegafur-based combination regimens (UFT, S-1) as effective adjuvant/palliative therapy for colon cancer, and this use is already standard practice in several markets — this is evidence consolidation of an existing indication rather than a speculative new use. However, the drug currently has zero marketing authorizations in Germany and lacks formal safety/label data.
To proceed, the following is needed:
- Official TFDA/BfArM package insert (warnings, contraindications) — currently a blocking data gap
- Confirmed drug-level MOA documentation from DrugBank to formally close the mechanism data gap
- DPD/DPYD deficiency screening protocol before recommending clinical use, given fluoropyrimidine class toxicity risk
- Regulatory pathway assessment given the drug is not currently marketed in Germany
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.