Tegafur

證據等級: L5

預測適應症: 10 個

Tegafur: From Gastric Cancer to Colonic Neoplasm

One-Sentence Summary

Tegafur is an oral fluoropyrimidine, a prodrug of 5-fluorouracil (5-FU), historically used to treat gastric cancer. The TxGNN model predicts strong applicability to Colonic Neoplasm, a prediction already backed by substantial real-world evidence — 30 registered clinical trials (including multiple completed Phase 3 RCTs) and 20 peer-reviewed publications, largely through the UFT (tegafur + uracil) adjuvant regimen.

Quick Overview

Item	Content
Original Indication	Gastric cancer (based on established pharmacology of tegafur monotherapy; formal Taiwan/Finland license text not available)
Predicted New Indication	Colonic Neoplasm
TxGNN Prediction Score	99.90%
Evidence Level	L1
Finland Market Status	未上市 (Not Marketed)
Number of Authorizations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available in the evidence pack (Data Gap DG002). Based on known pharmacology, tegafur is a prodrug of 5-FU, activated in the liver via CYP2A6, which inhibits thymidylate synthase and blocks DNA synthesis. It is part of the fluoropyrimidine antimetabolite class, both as monotherapy and as a component of the UFT combination (tegafur + uracil, where uracil inhibits dihydropyrimidine dehydrogenase [DPD] to increase 5-FU exposure). Its efficacy in gastric cancer has been well established, and mechanistically it extends directly to colonic neoplasm.

Gastric cancer and colonic neoplasm are both gastrointestinal malignancies that share the same pharmacological vulnerability to fluoropyrimidine-based DNA synthesis inhibition. In practice, the UFT regimen is already a standard postoperative adjuvant chemotherapy for colon cancer in multiple markets (notably Japan), meaning this is less a novel repurposing hypothesis and more a direct evidentiary extension of an already-established clinical use — which is reflected in the unusually large trial and literature base supporting this prediction.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00378716	Phase 3	Completed	1,608	UFT+leucovorin vs 5-FU+leucovorin, resected stage II/III colon cancer — head-to-head confirmatory trial
NCT00660894	Phase 3	Completed	1,535	UFT+leucovorin vs S-1 (TS-1) as adjuvant treatment for stage III colon cancer
NCT00392899	Phase 3	Completed	2,025	UFT adjuvant chemotherapy vs observation in curatively resected stage II colon cancer
NCT00152230	Phase 3	Completed	900	UFT postoperative adjuvant chemotherapy vs surgery alone, Dukes C colorectal cancer (NSAS-CC)
NCT00209742	Phase 3	Unknown	340	Comparison of UFT+LV, UFT+LV/UFT, and UFT+LV+PSK/UFT+PSK regimens, stage III colorectal cancer
NCT01918852	Phase 3	Completed	161	SALTO trial: S-1 vs capecitabine as first-line therapy in metastatic colorectal cancer
NCT00439517	Phase 2	Completed	302	FOLFOX-4+cetuximab vs UFOX (UFT-based)+cetuximab, first-line metastatic colorectal cancer
NCT02887365	Phase 4	Unknown	300	Tegafur-uracil as maintenance chemotherapy in stage II MSI-L/MSS colon cancer
NCT01225744	Phase 2	Completed	47	UFT + cetuximab/irinotecan/oxaliplatin, first-line metastatic colorectal cancer
NCT00890188	Phase 2	Unknown	34	UFT + thalidomide in advanced colorectal cancer after oxaliplatin-based chemotherapy

20 additional trials were retrieved but excluded from this table for brevity (see evidence pack for the complete list of 30).

Literature Evidence

PMID	Year	Type	Journal	Key Findings
33714860	2021	RCT	ESMO Open	ACTS-CC 02 trial, updated 5-year survival: S-1+oxaliplatin (SOX) not superior to UFT/LV as adjuvant therapy for high-risk stage III colon cancer
31917122	2020	RCT	Clin Colorectal Cancer	ACTS-CC 02 phase III trial: SOX vs UFT/LV as postoperative adjuvant chemotherapy, high-risk stage III colon cancer
33950962	2021	RCT	Medicine	Nationwide Taiwan cohort study and meta-analysis: UFT vs 5-FU as postoperative adjuvant chemotherapy, stage II/III colon cancer
15108041	2004	RCT	Int J Clin Oncol	RCT of adjuvant immunochemotherapy (OK-432) combined with oral pyrimidines including UFT in colorectal cancer
6402917	1983	RCT	Am J Clin Oncol	Comparative study of oral tegafur vs IV 5-FU in metastatic colorectal cancer
26347106	2015	RCT (Phase 3)	Ann Oncol	JFMC33-0502: randomized trial of treatment duration for UFT/LV adjuvant chemotherapy, stage IIB/III colon cancer
16648506	2006	RCT (Phase 3)	J Clin Oncol	NSABP C-06: oral UFT+LV vs IV 5-FU+LV, stage II/III colon carcinoma
38833114	2024	Prospective study	Int J Clin Oncol	JFMC46-1201 final analysis: UFT/LV adjuvant treatment for high-risk stage II colon cancer
25209093	2014	Review	Clin Colorectal Cancer	Asian consensus adaptation of international guidelines for metastatic colorectal cancer
17952521	2007	Review	Surgery Today	UFT as postoperative adjuvant chemotherapy for solid tumors: clinical evidence, mechanism of action, and future direction

10 additional publications were retrieved but excluded from this table for brevity (see evidence pack for the complete list of 20).

Finland Market Information

Tegafur currently has no marketing authorizations registered in Finland (market status: 未上市 / Not Marketed, 0 licenses on file).

Cytotoxicity

Tegafur is an antineoplastic agent (fluoropyrimidine class, 5-FU prodrug), so this section applies.

Item	Content
Cytotoxicity Classification	Conventional cytotoxic (fluoropyrimidine antimetabolite)
Myelosuppression Risk	Medium — leukopenia/neutropenia reported across UFT-based regimens; generally milder than IV 5-FU regimens
Emetogenicity Classification	Low to moderate (typical of oral fluoropyrimidines)
Monitoring Items	CBC with differential, liver and renal function, electrolytes; DPD/DPYD genotype status prior to initiation (per NCT05266300, DPYD-genotyping is used clinically to guide fluoropyrimidine dosing and avoid severe toxicity)
Handling Protection	Yes — must follow cytotoxic drug handling regulations despite oral route of administration

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 (evidence level L1) already establish UFT/tegafur-based regimens as effective adjuvant and metastatic-setting therapy for colon cancer, giving this prediction strong external validation rather than being a purely speculative signal. However, Finland-specific regulatory status, formal MOA documentation, and safety/package-insert data remain unavailable, blocking a full safety assessment.

To proceed, the following is needed:

TFDA/Fimea package insert — warnings, precautions, and contraindications (Blocking gap, DG001)
Formal mechanism of action documentation from DrugBank or equivalent source (DG002)
Confirmation of Finland market authorization pathway, since the drug is currently unmarketed there
DDI dataset (current query returned "not_found") and a DPD/DPYD-based dosing safety protocol before clinical use

Note: Nine other TxGNN-predicted indications for tegafur (e.g., cecum villous adenoma, colon leiomyoma, colonic lymphangioma) were also screened but carry evidence level L4–L5 with no or only tangential clinical/literature support and are recommended for Hold, not further evaluation at this time.

Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.