Tegafur
| Evidence Level: L1 | Predicted Indications: 10 |
Table of Contents
Tegafur: From Gastric Cancer to Colonic Neoplasm
One-Sentence Summary
Tegafur is an oral fluoropyrimidine prodrug of 5-fluorouracil (5-FU), historically used alone or as a component of combination regimens (UFT, S-1) for gastrointestinal cancers. The TxGNN model predicts it may be effective for Colonic Neoplasm, with 33 clinical trials and 22 publications currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not documented in this Evidence Pack’s EU regulatory data; literature indicates historical use as monotherapy/combination component for gastric and other GI cancers |
| Predicted New Indication | Colonic Neoplasm |
| TxGNN Prediction Score | 99.90% |
| Evidence Level | L1 |
| EU Market Status | ✗ Not Marketed |
| Number of Authorizations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, Tegafur is an oral prodrug of 5-fluorouracil (5-FU), a fluoropyrimidine antimetabolite that inhibits thymidylate synthase and disrupts DNA/RNA synthesis in rapidly dividing cells. It is commonly used as a component of combination regimens such as UFT (tegafur + uracil) and S-1 (tegafur + gimeracil + oteracil), which pair tegafur with agents that modulate 5-FU metabolism to improve efficacy and reduce gastrointestinal toxicity.
The literature evidence in this pack shows that tegafur-based regimens (UFT, S-1/TS-1) have already been extensively studied and used clinically for colorectal and colon cancer (e.g., adjuvant therapy for Stage II/III colon cancer, metastatic colorectal cancer), alongside their traditional use in gastric cancer. This means the “new” indication predicted by TxGNN — colonic neoplasm — substantially overlaps with an indication that is already well-established for tegafur-based combination products in several markets (notably Japan), even though a standalone EU authorization for Tegafur itself is not present in this dataset.
Mechanistically, gastric and colorectal cancers are both gastrointestinal adenocarcinomas that share similar sensitivity to fluoropyrimidine-based antimetabolite chemotherapy, which explains why a drug developed and validated for gastric cancer would show strong knowledge-graph proximity to colonic neoplasm. The very large volume of Phase 3 randomized trial data (UFT/LV, TS-1, S-1 regimens) for colon and colorectal cancer strongly corroborates this mechanistic plausibility, independent of the TxGNN score itself.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01918852 | Phase 3 | Completed | 161 | SALTO trial: S-1 vs capecitabine (± bevacizumab) as first-line treatment for metastatic colorectal cancer |
| NCT00660894 | Phase 3 | Completed | 1535 | UFT+leucovorin vs TS-1 as adjuvant treatment for Stage III colon cancer, with gene-expression predictive factor analysis |
| NCT00392899 | Phase 3 | Completed | 2025 | Adjuvant UFT vs observation after curative resection of Stage II colon cancer |
| NCT00152230 | Phase 3 | Completed | 900 | NSAS-CC trial: postoperative adjuvant UFT vs surgery alone in Dukes C colorectal cancer |
| NCT00378716 | Phase 3 | Completed | 1608 | Oral UFT+LV vs IV 5-FU+LV in resected Stage II/III colon cancer |
| NCT00905047 | Phase 3 | Completed | 89 | Crossover comparison of capecitabine (Xeloda) vs UFT+folinic acid in advanced/metastatic colorectal cancer |
| NCT03448549 | Phase 3 | Unknown | 1191 | SOX (S-1+oxaliplatin) vs XELOX as adjuvant chemotherapy for Stage III colorectal cancer |
| NCT00974389 | Phase 2 | Unknown | 40 | S-1 + bevacizumab in unresectable/recurrent colorectal cancer after prior chemotherapy failure |
| NCT01225744 | Phase 2 | Completed | 47 | Cetuximab + irinotecan + oxaliplatin + UFT as first-line treatment for metastatic colorectal cancer |
| NCT00439517 | Phase 2 | Completed | 302 | FOLFOX-4+cetuximab vs UFOX (UFT-based)+cetuximab as first-line therapy in metastatic colorectal cancer |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 31917122 | 2020 | RCT (Phase 3) | Clinical Colorectal Cancer | ACTS-CC 02 trial: S-1+oxaliplatin (SOX) vs UFT/LV as postoperative adjuvant chemotherapy in high-risk Stage III colon cancer |
| 33714860 | 2021 | RCT (5-year update) | ESMO Open | Updated 5-year overall survival and subgroup analysis of the ACTS-CC 02 trial (SOX vs UFT/LV) |
| 16648506 | 2006 | RCT | Journal of Clinical Oncology | NSABP C-06: oral UFT+LV vs IV 5-FU+LV in Stage II/III colon carcinoma, comparable disease-free and overall survival |
| 26347106 | 2015 | RCT | Annals of Oncology | JFMC33-0502: optimal treatment duration for oral UFT+LV adjuvant chemotherapy in Stage IIB/III colon cancer |
| 15108041 | 2004 | RCT | International Journal of Clinical Oncology | Adjuvant immunochemotherapy combining UFT with OK-432 in colorectal cancer |
| 35168560 | 2022 | Prospective observational study | BMC Cancer | JFMC46-1201: UFT/LV efficacy in high-risk Stage II colon cancer using propensity score matching |
| 38833114 | 2024 | Prospective controlled trial (final analysis) | International Journal of Clinical Oncology | Final 5-year survival results confirming UFT/LV benefit in high-risk Stage II colon cancer |
| 33950962 | 2021 | Nationwide cohort study / meta-analysis | Medicine | UFT vs 5-FU as postoperative adjuvant chemotherapy in Stage II/III colon cancer, Taiwan NHIRD data |
| 25209093 | 2014 | Review | Clinical Colorectal Cancer | Asian consensus guidelines for metastatic colorectal cancer treatment |
| 17952521 | 2007 | Review | Surgery Today | UFT (tegafur+uracil) as postoperative adjuvant chemotherapy across solid tumours including colon/rectum, with mechanism of action discussion |
EU Market Information
Tegafur currently holds no marketing authorisation in the EU as a standalone active substance (0 authorizations recorded). It is only available clinically as part of fixed-dose combination products (e.g., UFT, S-1/Teysuno), which are tracked separately and are not covered by this Evidence Pack.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (fluoropyrimidine class; prodrug of 5-fluorouracil) |
| Myelosuppression Risk | Medium — neutropenia and leukopenia are recognized class effects of fluoropyrimidines, generally milder with oral tegafur-based regimens than IV 5-FU |
| Emetogenicity Classification | Low to moderate |
| Monitoring Items | Complete blood count with differential, liver and renal function, and DPYD/DPD status given known dihydropyrimidine dehydrogenase (DPD)-related toxicity risk in fluoropyrimidines |
| Handling Protection | Must follow standard cytotoxic drug handling and disposal protocols |
Safety Considerations
Please refer to the SmPC for safety information. No drug interaction data, warnings, or contraindications were available in this Evidence Pack.
Conclusion and Next Steps
Decision: Hold
Rationale:
- The clinical trial and literature evidence for tegafur-based regimens in colon/colorectal cancer is strong (L1: multiple completed Phase 3 RCTs), but Tegafur has no EU marketing authorization (0 licenses), and a Blocking data gap on TFDA/SmPC warnings and contraindications currently prevents the mandatory S1 safety pre-assessment.
To proceed, the following is needed:
- TFDA/SmPC label data (warnings, contraindications) — download and parse the official product label PDF
- Detailed mechanism of action (MOA) data via DrugBank API query
- Clarification of Tegafur’s regulatory status as a standalone substance vs. its role in combination products (UFT, S-1) authorized in the EU
- A DPD (DPYD) deficiency screening protocol, given the well-documented fluoropyrimidine toxicity risk highlighted in the trial evidence
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.