Tegafur
| 證據等級: L5 | 預測適應症: 10 個 |
目錄
Tegafur: From Established Fluoropyrimidine Chemotherapy to Colonic Neoplasm
One-Sentence Summary
Tegafur is an oral prodrug of 5-fluorouracil, most widely known as a component of combination regimens such as UFT (tegafur/uracil) and S-1 (tegafur/gimeracil/oteracil), used broadly in gastrointestinal and other solid tumors. The TxGNN model predicts high relevance for Colonic Neoplasm, and this is strongly supported by 31 clinical trials (multiple completed Phase 3 RCTs) and 20 publications — though the evidence indicates this is an already-established clinical use rather than a genuinely novel repurposing signal.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not formally recorded in the regulatory dataset (no approved license on file). Based on known pharmacology, tegafur is a 5-FU prodrug used clinically as a component of UFT/S-1 combinations across gastric, colorectal, breast, and lung cancers |
| Predicted New Indication | Colonic Neoplasm |
| TxGNN Prediction Score | 99.90% |
| Evidence Level | L1 |
| Norway Market Status | ✗ Not Marketed |
| Number of Authorizations | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Formal mechanism-of-action documentation was not retrievable from DrugBank in this evidence pack (flagged as a High-severity data gap, DG002). Based on the available evidence-pack rationale, tegafur is metabolized in the liver via CYP2A6 to its active moiety, 5-fluorouracil, which inhibits thymidylate synthase and disrupts DNA synthesis — a cytotoxic mechanism broadly effective against highly proliferative malignancies, including colorectal cancer.
Importantly, the evidence pack itself flags a critical caveat: tegafur (as UFT or S-1) already carries an established, guideline-recognized role in colon and colorectal cancer treatment — most visibly as adjuvant therapy after curative resection and in metastatic settings. The very large body of completed Phase 3 RCTs below reflects decades of confirmed clinical use rather than a newly-discovered signal. In other words, the TxGNN model's high score for "colonic neoplasm" is best interpreted as validation of known pharmacology, not as a novel drug-repurposing opportunity. This distinction should inform how much strategic weight is placed on this candidate versus genuinely new signals.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00378716 | Phase 3 | Completed | 1,608 | UFT+leucovorin vs 5-FU+leucovorin, head-to-head in resected stage II/III colon cancer |
| NCT00152230 | Phase 3 | Completed | 900 | UFT postoperative adjuvant chemotherapy vs surgery alone (Dukes C colorectal cancer, NSAS-CC) |
| NCT00392899 | Phase 3 | Completed | 2,025 | UFT adjuvant chemotherapy vs observation in curatively resected stage II colon cancer |
| NCT00660894 | Phase 3 | Completed | 1,535 | UFT+leucovorin vs S-1 as adjuvant treatment for stage III colon cancer |
| NCT00209742 | Phase 3 | Unknown | 340 | Multi-arm comparison of UFT+LV / UFT+LV+PSK regimens for stage III colorectal cancer |
| NCT01918852 | Phase 3 | Completed | 161 | SALTO trial: S-1 (tegafur-based) vs capecitabine as first-line therapy in metastatic colorectal cancer |
| NCT03448549 | Phase 3 | Unknown | 1,191 | S-1+oxaliplatin (SOX) vs capecitabine+oxaliplatin (XELOX) adjuvant therapy for stage III colorectal cancer |
| NCT01225744 | Phase 2 | Completed | 47 | UFT + cetuximab + irinotecan + oxaliplatin in first-line metastatic colorectal cancer |
| NCT00002801 | Phase 1 | Completed | 30 | UFT + leucovorin + radiotherapy postoperatively for rectal cancer |
| NCT05266300 | N/A | Completed | 722 | Clinical implementation of DPYD genotyping in patients treated with fluoropyrimidines (incl. tegafur), safety/pharmacogenomics focus |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 31917122 | 2020 | RCT | Clinical Colorectal Cancer | ACTS-CC 02 Phase III trial: S-1+oxaliplatin vs UFT/LV as postoperative adjuvant therapy in high-risk stage III colon cancer |
| 33714860 | 2021 | RCT | ESMO Open | Updated 5-year survival analysis of ACTS-CC 02; SOX not superior to UFT/LV on disease-free survival |
| 33950962 | 2021 | RCT | Medicine | Nationwide cohort study and meta-analysis: UFT vs 5-FU as postoperative adjuvant chemotherapy in stage II/III colon cancer |
| 15108041 | 2004 | RCT | Int J Clin Oncol | Adjuvant immunochemotherapy trial combining OK-432 with UFT and HCFU in colorectal cancer |
| 16648506 | 2006 | RCT | J Clin Oncol | NSABP C-06: oral UFT+leucovorin vs IV 5-FU+leucovorin in stage II/III colon carcinoma |
| 26347106 | 2015 | RCT | Annals of Oncology | JFMC33-0502 Phase III trial on treatment duration of UFT/LV adjuvant therapy for stage IIB/III colon cancer |
| 25209093 | 2014 | Review | Clinical Colorectal Cancer | Asian consensus guideline adaptation for metastatic colorectal cancer management |
| 17952521 | 2007 | Review | Surgery Today | Review of UFT clinical evidence, mechanism of action, and future directions in adjuvant chemotherapy for solid tumors |
| 6402917 | 1983 | Cohort | Am J Clin Oncol | Comparative study of oral tegafur vs IV 5-fluorouracil in metastatic colorectal cancer |
| 7990476 | 1994 | Cohort | J Surg Oncol | Effects of preoperative UFT chemotherapy on DNA ploidy, cell cycle, and histology in gastric/colonic cancer |
Norway Market Information
Tegafur is currently not marketed in Norway, and no drug authorization records are available in this evidence pack.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (fluoropyrimidine class; 5-FU prodrug) |
| Myelosuppression Risk | Medium — fluoropyrimidines are associated with neutropenia and leukopenia; DPYD-deficient patients are at markedly elevated risk (see NCT05266300 genotyping study) |
| Emetogenicity Classification | Low to moderate |
| Monitoring Items | CBC with differential, liver and renal function, electrolytes; DPYD genotype/phenotype status where available to reduce severe toxicity risk |
| Handling Protection | Must follow institutional cytotoxic/hazardous drug handling regulations |
Safety Considerations
Please refer to the package insert for safety information. No structured warnings, contraindications, or drug-interaction data were available in this evidence pack; the absence of Norwegian product-label warnings/contraindications is flagged as a Blocking data gap (DG001) that must be resolved before final safety sign-off.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: The colonic neoplasm signal is backed by an unusually large and mature evidence base — multiple completed Phase 3 RCTs (some with >1,500 patients) and consistent literature support (L1) — but this reflects confirmation of an already-established use of tegafur/UFT/S-1 in colorectal cancer, not a new discovery. The other nine predicted indications in this pack (villous adenoma, NET G1, lipoma, leiomyoma, lymphangioma, hemangioma, etc.) have negligible-to-weak evidence (L4–L5) and are mechanistically implausible for a cytotoxic agent, and should remain on Hold.
To proceed, the following is needed:
- Resolve DG001 (Blocking): obtain formal product-label warnings/contraindications before any S1 safety review
- Resolve DG002 (High): confirm mechanism-of-action documentation via DrugBank API
- Clarify regulatory pathway: since tegafur holds zero authorizations in Norway, determine whether market entry (rather than "repurposing") is the actual strategic question
- Reassess portfolio priority: given this candidate largely reconfirms known clinical practice, consider whether resources are better directed toward genuinely novel signals elsewhere in the prediction set
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.