Uracil
| Evidence Level: L3 | Predicted Indications: 10 |
Table of Contents
Uracil: From an Unspecified Approved Indication (UFT Component) to Colonic Neoplasm
One-Sentence Summary
Uracil is the uracil component of UFT (tegafur-uracil), an oral anticancer combination marketed in Singapore as UFT Capsule. The TxGNN model predicts it may be effective for colonic neoplasm. The supporting evidence is indirect: 1 registered clinical trial (which does not test uracil) and 20 publications, most of which concern the UFT combination rather than uracil alone.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the Singapore licence record (UFT is used as an oral fluoropyrimidine anticancer therapy) |
| Predicted New Indication | Colonic neoplasm |
| TxGNN Prediction Score | 99.50% |
| Evidence Level | L3 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Hold (treat as a research question) |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the compiled drug record. Based on the literature, uracil is the component of UFT (tegafur and uracil in a 4:1 molar ratio) that competitively inhibits dihydropyrimidine dehydrogenase (DPD). Tegafur is a prodrug of 5-fluorouracil (5-FU). By blocking 5-FU breakdown, uracil raises 5-FU levels in blood and tumour tissue, which is a plausible mechanism in colorectal cancer.
UFT has been studied as postoperative adjuvant chemotherapy in colon and rectal cancer, and the literature includes reviews, a Taiwanese nationwide cohort study with meta-analysis comparing UFT with 5-FU, and a phase III trial using UFT/leucovorin as the comparator arm. However, this evidence comes from the combination product. No data show uracil acting as a single agent against colon cancer.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT04164069 | Phase 1 | Completed | 9 | Dasatinib to prevent oxaliplatin-induced neuropathy in metastatic GI cancer patients on FOLFOX. It does not evaluate uracil or UFT; the link is indirect, through the chemotherapy backbone. |
Literature Evidence
Publications on the combination product, ordered by study type. Many other retrieved papers are preclinical or about folate and DNA repair, and are omitted as only loosely related.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 31917122 | 2020 | Phase III RCT | Clin Colorectal Cancer | ACTS-CC 02: S-1 plus oxaliplatin compared with UFT/LV as adjuvant therapy in high-risk stage III colon cancer |
| 33714860 | 2021 | Phase III RCT (updated) | ESMO Open | 5-year survival update: SOX was not superior to UFT/LV for disease-free survival |
| 33950962 | 2021 | Cohort study and meta-analysis | Medicine | UFT versus 5-FU as adjuvant therapy in stage II/III colon cancer, using Taiwan national insurance data |
| 15108041 | 2004 | RCT | Int J Clin Oncol | Adjuvant chemotherapy with or without OK-432 immunotherapy, using UFT or carmofur, in colorectal cancer |
| 17952521 | 2007 | Review | Surg Today | UFT as postoperative adjuvant chemotherapy: clinical evidence and mechanism of action |
| 25209093 | 2014 | Review | Clin Colorectal Cancer | Asian consensus guidelines for metastatic colorectal cancer |
| 11273592 | 2001 | Review | Semin Oncol | NSABP adjuvant trials in colon cancer |
| 12601545 | 2003 | Case report | Int J Clin Oncol | Therapy-related erythroleukaemia after UFT and mitomycin C in a colon cancer patient |
| 11320674 | 2001 | Case report | Cancer Chemother Pharmacol | UFT-induced haemolytic anaemia in metastatic colon cancer |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN03692P | UFT CAPSULE (Taiho Pharmaceutical) | Capsule (oral) | Not recorded in the licence data |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (fluoropyrimidine class; UFT delivers 5-FU through tegafur, with uracil as a DPD inhibitor) |
| Myelosuppression Risk | Medium. Case reports describe pancytopenia, erythroleukaemia and haemolytic anaemia during UFT treatment; reviews describe a generally mild toxicity profile |
| Emetogenicity Classification | Low to medium (typical of oral fluoropyrimidines) |
| Monitoring Items | CBC with differential, liver and renal function |
| Handling Protection | Follow institutional cytotoxic drug handling regulations. Please refer to the package insert warnings and precautions |
Safety Considerations
- Reported adverse events (from case reports on UFT-containing therapy): haemolytic anaemia, and therapy-related erythroleukaemia after prolonged UFT combined with mitomycin C.
Please refer to the package insert for full safety information. Warnings, contraindications and drug interaction data were not available in the data compiled for this report.
Conclusion and Next Steps
Decision: Hold (research question)
Rationale: The mechanism is plausible and UFT has a long record in colorectal cancer. However, the only registered trial does not test uracil, the evidence comes from the combination product, and no Phase 3 RCT of uracil alone supports the colonic neoplasm prediction. Safety and mechanism data are also incomplete. Uracil's role as a DPD inhibitor within UFT is already part of its existing use, so this is better read as a confirmation of UFT's known colorectal activity than as a new repurposing signal for uracil itself.
To proceed, the following is needed:
- The Singapore package insert (approved indications, warnings, contraindications), so that safety screening can be completed
- Mechanism of action data from DrugBank
- Clarification of whether the intended product is UFT (tegafur-uracil) or uracil alone, and of any local colorectal indication
- Review of the primary UFT adjuvant trials in colorectal cancer to establish an evidence level based on the combination
- A DPD deficiency testing and monitoring plan
Other predicted indications (briefly):
- Gastric carcinoma (score 99.46%, evidence L3): Phase II studies and one Phase III RCT (SAMIT, UFT or S-1 as adjuvant therapy) support UFT-based regimens. Neither of the two listed registered trials tests uracil.
- Rectosigmoid junction neoplasm and cecal disease (L4): only case reports or unrelated trials, so Hold.
- Lipoma of colon, colonic lymphangioma, cecum villous adenoma, cecum neuroendocrine tumour G1, cavernous hemangioma of colon, colon leiomyoma (L5): no mechanistic rationale or supporting evidence; they appear to reflect graph proximity to colon cancer only. Hold.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.