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), originally used to treat gastric cancer. The TxGNN model predicts it may be effective for colonic neoplasm, with 16 clinical trials (including several completed Phase 3 trials) and 20 publications currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Gastric cancer (approved indication text is not listed in the Singapore licence records; gastric cancer is taken from the knowledge-graph indication data) |
| Predicted New Indication | Colonic neoplasm |
| TxGNN Prediction Score | 99.90% |
| Evidence Level | L1 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 3 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on established pharmacology, tegafur is an oral prodrug of 5-FU, converted mainly in the liver by CYP2A6. As a fluoropyrimidine, it inhibits thymidylate synthase and is incorporated into RNA and DNA, which disrupts the growth of dividing tumour cells.
Gastric cancer and colonic neoplasm are both gastrointestinal adenocarcinomas, and fluoropyrimidines are a standard backbone of treatment for both. When tegafur is combined with uracil (UFT), DPD-mediated breakdown of 5-FU is inhibited. With leucovorin, the thymidylate synthase complex is stabilised. The same drug action is therefore relevant to colorectal cancer. This mechanistic reasoning is inferred from known pharmacology and not from the supplied mechanism field.
Clinical Trial Evidence
The table lists the 10 most relevant of the 16 trials. Several trials test tegafur-containing regimens (UFT or S-1) rather than tegafur alone.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00378716 | Phase 3 | Completed | 1608 | Oral UFT + leucovorin vs 5-FU/LV in resected stage II/III colon cancer |
| NCT00152230 | Phase 3 | Completed | 900 | Postoperative adjuvant UFT vs surgery alone in Dukes C colorectal cancer |
| NCT00392899 | Phase 3 | Completed | 2025 | Adjuvant UFT vs observation in curatively resected stage II colon cancer |
| NCT00660894 | Phase 3 | Completed | 1535 | UFT + leucovorin vs S-1 as adjuvant treatment for stage III colon cancer |
| NCT03448549 | Phase 3 | Unknown | 1191 | SOX (S-1 + oxaliplatin) vs XELOX as adjuvant chemotherapy for stage III colorectal cancer |
| NCT00385970 | Phase 3 | Unknown | 380 | UFT + PSK vs UFT + leucovorin as adjuvant therapy in stage IIB/III colorectal cancer |
| NCT00209742 | Phase 3 | Unknown | 340 | Three postoperative UFT-based regimens in stage III colorectal cancer |
| NCT00905047 | Phase 3 | Completed | 89 | Patient preference crossover, Xeloda vs UFT + folinic acid, in advanced/metastatic colorectal cancer |
| NCT02887365 | Phase 4 | Unknown | 300 | Tegafur-uracil maintenance in stage II MSS/MSI-L colon cancer |
| NCT01225744 | Phase 2 | Completed | 47 | UFT with cetuximab, irinotecan and oxaliplatin as first-line therapy for metastatic colorectal cancer |
Literature Evidence
The table lists 10 of the 20 publications, prioritising randomised trials, then reviews and cohort studies.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 31917122 | 2020 | RCT | Clin Colorectal Cancer | ACTS-CC 02: S-1 + oxaliplatin vs UFT/LV as adjuvant therapy in high-risk stage III colon cancer |
| 33714860 | 2021 | RCT | ESMO Open | Updated 5-year survival of ACTS-CC 02. SOX was not superior to UFT/LV for disease-free survival |
| 33950962 | 2021 | Cohort study and meta-analysis | Medicine | Taiwan nationwide cohort and meta-analysis of UFT vs 5-FU as adjuvant therapy in stage II/III colon cancer |
| 10089948 | 1999 | Meta-analysis | Jpn J Clin Oncol | Individual patient data meta-analysis of randomised trials of oral fluoropyrimidines as adjuvant therapy in colorectal cancer |
| 17952521 | 2007 | Review | Surg Today | UFT as postoperative adjuvant chemotherapy for solid tumours: clinical evidence, mechanism and future direction |
| 36676634 | 2022 | Cohort study | Medicina (Kaunas) | Benefit of UFT as postoperative adjuvant chemotherapy for stage IIA colon cancer, using Taiwan national data |
| 6402917 | 1983 | Randomised study | Am J Clin Oncol | Oral tegafur vs intravenous 5-FU in metastatic colorectal cancer |
| 25209093 | 2014 | Guideline/Consensus | Clin Colorectal Cancer | Asian consensus on adapting international guidelines for metastatic colorectal cancer |
| 16111469 | 2005 | Review | Expert Rev Anticancer Ther | Stage-specific chemotherapy options in colon cancer |
| 11320674 | 2001 | Case report | Cancer Chemother Pharmacol | UFT-induced haemolytic anaemia in a patient with metastatic colon cancer |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN03692P | UFT CAPSULE | Capsule | Not listed in the licence record |
| SIN13672P | TS-ONE Capsule 20 | Capsule | Not listed in the licence record |
| SIN13673P | TS-ONE Capsule 25 | Capsule | Not listed in the licence record |
All three licences are valid single-ingredient registrations held by Taiho Pharmaceutical.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (fluoropyrimidine class, oral 5-FU prodrug) |
| Myelosuppression Risk | Medium (haematological toxicity is expected with fluoropyrimidines; please refer to the package insert) |
| Emetogenicity Classification | Low to medium |
| Monitoring Items | Complete blood count with differential, liver and renal function, electrolytes |
| Handling Protection | Follow cytotoxic drug handling regulations |
Safety Considerations
- Adverse event reports: The literature includes case reports of haemolytic anaemia with UFT and hypertriglyceridaemia with S-1.
- Please refer to the package insert for warnings, contraindications and drug interaction information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Several completed Phase 3 randomised trials (for example NCT00378716, NCT00152230, NCT00392899 and NCT00660894) have tested tegafur-containing regimens in colon and colorectal cancer, which supports an L1 evidence level. However, most of this evidence concerns combinations (UFT, S-1) rather than tegafur alone. Safety label data and mechanism of action data are also missing from the compiled data.
To proceed, the following is needed:
- Singapore package insert warnings and contraindications (a blocking gap for safety screening)
- Mechanism of action data from DrugBank
- Confirmation of the approved indications for the three Singapore licences
- Review of which regimens (UFT/leucovorin or S-1-based) are applicable to Singapore practice
- A safety monitoring plan, including haematological and liver and renal function monitoring
Other predicted indications: The other nine predictions (cecum villous adenoma, cecum neuroendocrine tumor G1, lipoma of colon, cecal disease, colon leiomyoma, benign neoplasm of cecum, rectosigmoid junction neoplasm, colonic lymphangioma and cavernous hemangioma of colon) have no direct tegafur evidence. Most are benign lesions where chemotherapy is not plausible, so they are on Hold. The rectosigmoid junction neoplasm is treated as a research question, because colorectal adenocarcinoma evidence may apply indirectly.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.