Tegafur

證據等級: L5

預測適應症: 10 個

Tegafur: From Gastrointestinal Cancer Chemotherapy to Colonic Neoplasm

One-Sentence Summary

Tegafur is a fluoropyrimidine prodrug serving as the active core of well-established oral chemotherapy combinations (UFT and S-1) for gastrointestinal cancers. The TxGNN model predicts it may be effective for Colonic Neoplasm, with 30 clinical trials and 20 publications currently supporting this direction.

Quick Overview

Item	Content
Original Indication	Not available (no Philippines registration record)
Predicted New Indication	Colonic Neoplasm
TxGNN Prediction Score	99.90%
Evidence Level	L1
Philippines Market Status	✗ Not Marketed
Number of Registrations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available in the regulatory record. Based on known pharmacological information, Tegafur is a prodrug of 5-fluorouracil (5-FU) and serves as the active fluoropyrimidine component in two widely used oral chemotherapy combinations: UFT (tegafur + uracil) and S-1 (tegafur + gimeracil + oteracil). After oral administration, tegafur is enzymatically converted to 5-FU, which inhibits thymidylate synthase (TS) — blocking dTMP synthesis required for DNA replication — and is incorporated into RNA to disrupt transcription.

Colonic neoplasms show characteristically high TS expression, conferring well-documented sensitivity to 5-FU–class drugs. This mechanistic pathway is essentially identical to the established anti-gastrointestinal cancer activity of tegafur-based regimens, meaning the biological rationale for the predicted indication is direct and not extrapolated from distant tumor biology.

The clinical evidence base strongly validates the TxGNN prediction. Multiple large Phase 3 RCTs have evaluated UFT + leucovorin and S-1 in both adjuvant (Stage II/III) and metastatic colorectal cancer settings, involving thousands of patients. The model’s top-ranked prediction mirrors an indication for which tegafur-based regimens are already a de facto standard in parts of Asia.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00378716	Phase 3	Completed	1,608	NSABP C-06: Oral UFT + leucovorin vs. weekly IV 5-FU + leucovorin in resected Stage II/III colon cancer; established non-inferiority of oral tegafur-based regimen for DFS and OS
NCT00392899	Phase 3	Completed	2,025	Adjuvant tegafur-uracil vs. observation after curative resection for Stage II colon cancer; assessed whether adjuvant fluoropyrimidine chemotherapy adds meaningful survival benefit
NCT00660894	Phase 3	Completed	1,535	Head-to-head RCT of UFT + leucovorin vs. S-1 as adjuvant therapy for Stage III colon cancer, with gene expression biomarker sub-study
NCT00152230	Phase 3	Completed	900	NSAS-CC: UFT vs. surgery alone as postoperative adjuvant chemotherapy for Dukes C (Stage III) colorectal cancer; evaluated relapse-free and overall survival over 5-year follow-up
NCT01918852	Phase 3	Completed	161	SALTO trial: S-1 (tegafur-based) vs. capecitabine as first-line therapy for metastatic colorectal cancer; direct head-to-head safety and efficacy comparison of oral fluoropyrimidines
NCT03448549	Phase 3	Unknown	1,191	Large RCT comparing SOX (S-1 + oxaliplatin) vs. XELOX as adjuvant chemotherapy for Stage III colorectal cancer; addresses hand-foot syndrome burden as a secondary endpoint
NCT00209742	Phase 3	Unknown	340	Three-arm postoperative adjuvant study (UFT+LV vs. UFT+LV/UFT vs. UFT+LV+PSK/UFT+PSK) for Stage III colorectal cancer; compared DFS, OS, and quality of life
NCT00497107	Phase 3	Unknown	300	Randomized comparison of UFT/LV vs. UFT/LV + PSK as postoperative adjuvant therapy for Stage IIIa/b colorectal cancer; 3-year DFS as primary endpoint
NCT00524706	Phase 1/2	Unknown	42	SOL regimen (S-1 + oral leucovorin + oxaliplatin) dose-finding and efficacy exploration in untreated metastatic colorectal cancer; established S-1 as viable substitute for IV 5-FU/LV
NCT05266300	N/A	Completed	722	Clinical implementation of DPYD genotyping in fluoropyrimidine-treated patients (explicitly including tegafur); demonstrated significant toxicity risk reduction with pre-treatment pharmacogenomic screening

Literature Evidence

PMID	Year	Type	Journal	Key Findings
31917122	2020	RCT	Clinical Colorectal Cancer	ACTS-CC 02 Phase III trial: SOX (S-1 + oxaliplatin) vs. UFT/LV as adjuvant therapy for high-risk Stage III colon cancer; primary endpoint DFS
33714860	2021	RCT	ESMO Open	Updated 5-year survival from ACTS-CC 02; SOX was not superior to UFT/LV for DFS, confirming UFT/LV as a durable adjuvant standard for high-risk Stage III
33950962	2021	RCT / Meta-analysis	Medicine	Nationwide cohort (Taiwan NHIRD) + meta-analysis comparing UFT vs. IV 5-FU as postoperative adjuvant chemotherapy for Stage II/III colon cancer; multivariate Cox regression DFS/OS analysis
16648506	2006	RCT	J Clinical Oncology	NSABP C-06 full report: oral UFT + LV vs. weekly IV 5-FU + LV in Stage II/III colon cancer; primary analysis of DFS and OS after surgery
15108041	2004	RCT	Int J Clinical Oncology	Randomized trial of adjuvant immunochemotherapy combinations including UFT (tegafur/uracil) for colorectal cancer; evaluated OK-432 + UFT vs. carmofur-based regimens
25209093	2014	Review	Clinical Colorectal Cancer	Asian multidisciplinary consensus guidelines (23 experts, 10 countries) adapting international mCRC recommendations; includes S-1/UFT-based regimen positioning
17952521	2007	Review	Surgery Today	Comprehensive review of UFT as postoperative adjuvant chemotherapy across solid tumors; summarizes mechanism, trial results, and future directions for colon/rectal cancer
6402917	1983	Comparative Study	Am J Clinical Oncology	Early randomized study of oral tegafur vs. IV 5-FU in measurable metastatic colorectal cancer; demonstrated comparable partial response rates supporting oral tegafur as an alternative
3933845	1985	Animal Study	Bull Tokyo Med Dental Univ	DMH-induced murine colonic cancer model: levamisole + tegafur combination produced longer survival and fewer distant metastases than either agent alone
6777388	1980	Preclinical	J Cancer Res Clin Oncol	Chemoprevention study in carcinogen-induced (MNU) colonic tumors in rats; tegafur (ftorafur) significantly reduced tumor incidence over 10-week treatment, establishing early mechanistic proof

Philippines Market Information

Tegafur currently has no registered products in the Philippines. There are no active regulatory authorizations on file.

Should clinical use be pursued, an importation license or compassionate/special use pathway would need to be established through the FDA Philippines. Reference products available in neighboring markets include UFT capsules (marketed in Japan and Taiwan) and S-1 tablets (Teysuno, marketed in the EU; TS-1, marketed in Japan and Taiwan).

Cytotoxicity

Tegafur is a conventional cytotoxic agent of the fluoropyrimidine class.

Item	Content
Cytotoxicity Classification	Conventional cytotoxic — Fluoropyrimidine prodrug (5-FU class)
Myelosuppression Risk	Moderate — neutropenia and thrombocytopenia are established class effects; UFT and S-1 formulations typically show lower myelosuppression rates compared to IV 5-FU
Emetogenicity Classification	Low to moderate
Monitoring Items	CBC with differential (baseline and each cycle), liver function (ALT, AST, bilirubin), renal function (creatinine, eGFR), electrolytes; pre-treatment DPYD genotyping strongly recommended
Handling Protection	Must follow cytotoxic drug handling regulations (closed-system transfer devices, appropriate PPE for preparation and disposal)

Safety Considerations

Formal safety data (package insert warnings, contraindications, and drug–drug interaction profile) are not available in the current evidence pack. Please refer to the reference product package inserts (UFT, Teysuno/TS-1) for full safety information.

Two clinically relevant signals from the literature warrant proactive attention:

DPYD deficiency: Pre-treatment DPYD genotyping is recommended before initiating any fluoropyrimidine therapy, including tegafur-based regimens. A clinical implementation study (NCT05266300, n=722) demonstrated meaningful toxicity reduction with systematic genotyping.
Hemolytic anemia: At least one case of UFT-induced hemolytic anemia in a metastatic colon cancer patient has been published (PMID 11320674), representing a rare but serious adverse event not previously attributed to this drug class.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: Tegafur has one of the strongest evidence bases among drug repurposing candidates: colonic neoplasm is supported by at least six completed Phase 3 RCTs involving over 8,000 cumulative patients across adjuvant and metastatic settings, alongside a directly validated mechanistic link through 5-FU/TS inhibition. The L1 evidence level reflects genuine clinical-grade validation, not extrapolation. The primary barriers are regulatory (no Philippines registration) and safety documentation gaps, not scientific uncertainty.

To proceed, the following is needed:

Regulatory pathway determination: FDA Philippines importation license or compassionate-use authorization for UFT capsules or S-1 tablets
Full package insert review for contraindications, key warnings, and drug–drug interactions (TFDA, EMA, or PMDA monographs available as reference)
Pre-treatment DPYD genotyping protocol — particularly important given the CYP2A6/DPD polymorphism variability in Filipino patients
Local pharmacokinetic considerations: CYP2A6 and DPD activity differences in Asian populations may affect tegafur-to-5-FU conversion rate and require dose individualization
Safety monitoring schedule: CBC and liver/renal function testing at defined intervals per cycle
Supply chain verification: confirm formulation availability (UFT or S-1) and cold chain/storage requirements in the Philippines market context
Disclaimer

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