Oteracil
| 證據等級: L5 | 預測適應症: 10 個 |
目錄
Oteracil: From Gastric Cancer to Colonic Neoplasm
One-Sentence Summary
Oteracil is a non-cytotoxic modulating component of the S-1 combination (tegafur/gimeracil/oteracil), historically used alongside tegafur-based regimens in gastric and gastrointestinal cancers. The TxGNN model predicts it may be effective for Colonic Neoplasm, with 8 clinical trials and 20 publications currently supporting this direction, including three completed Phase 3 RCTs.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Gastric cancer (as a component of the S-1 combination) — specific Fimea/TFDA label text not available |
| Predicted New Indication | Colonic Neoplasm |
| TxGNN Prediction Score | 99.99% |
| Evidence Level | L1 |
| Finland Market Status | ✗ Not Marketed |
| Number of Authorizations | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data for oteracil itself is not available. Based on known information, oteracil is part of the S-1 oral fluoropyrimidine combination (tegafur + gimeracil + oteracil). Within this combination, oteracil acts by inhibiting orotate phosphoribosyltransferase (OPRT) in the gastrointestinal tract, which reduces local phosphorylation of 5-FU generated from tegafur and thereby lowers GI toxicity — it does not itself exert direct antitumor activity.
Gastric cancer and colonic neoplasm are both gastrointestinal malignancies that share the same underlying pharmacological target: the fluoropyrimidine (5-FU) pathway delivered via tegafur. Because S-1 has already been established and, in several countries, approved for colorectal cancer in addition to gastric cancer, the mechanistic rationale for extending oteracil-containing regimens to colonic neoplasm is well supported.
The strength of this prediction rests specifically on the S-1 combination's extensive clinical development in colorectal cancer (ACTS-CC, ACTS-RC, SALTO trials), rather than on any independent activity of oteracil. This distinguishes it from several lower-ranked predictions in this evidence pack (e.g., benign or vascular colonic lesions), which lack any plausible cytotoxic mechanism and appear to be anatomical-proximity artifacts of the TxGNN embedding rather than genuine pharmacological signals.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00660894 | Phase 3 | Completed | 1535 | UFT+Leucovorin vs. TS-1 (S-1) as adjuvant treatment for Stage III colon cancer, with gene-expression predictive factor analysis |
| NCT01918852 | Phase 3 | Completed | 161 | SALTO study: S-1 vs. Capecitabine as first-line treatment for metastatic colorectal cancer, ± bevacizumab |
| NCT03448549 | Phase 3 | Unknown | 1191 | SOX (oxaliplatin + S-1) vs. XELOX as adjuvant chemotherapy for Stage III colorectal cancer |
| NCT06255379 | Phase 2 | Not yet recruiting | 52 | Fuquinitinib combined with S-1 (tegafur/gimeracil/oteracil) as third-line treatment for advanced metastatic CRC |
| NCT02618356 | Phase 2 | Unknown | 82 | Raltitrexed + S-1 for metastatic colorectal cancer that failed standard chemotherapy; primary endpoint mPFS |
| NCT00974389 | Phase 2 | Unknown | 40 | S-1 + bevacizumab in unresectable/recurrent colorectal cancer after irinotecan/oxaliplatin failure |
| NCT00524706 | Phase 1/2 | Unknown | 42 | S-1 + oral leucovorin + oxaliplatin (SOL regimen) for untreated metastatic colorectal cancer |
| NCT02216149 | Phase 2 | Terminated | 20 | S-1/capecitabine + oxaliplatin vs. cardiac microvascular safety in metastatic GI adenocarcinoma (safety-focused, not efficacy) |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 31917122 | 2020 | RCT | Clin Colorectal Cancer | ACTS-CC 02: S-1 + oxaliplatin (SOX) superior to UFT/LV as adjuvant therapy in high-risk Stage III colon cancer |
| 27056996 | 2016 | RCT | Annals of Oncology | ACTS-RC (JFMC35-C1): S-1 vs. UFT as adjuvant chemotherapy for Stage II/III rectal cancer |
| 24942277 | 2014 | RCT | Annals of Oncology | ACTS-CC trial: S-1 non-inferior to UFT/LV as adjuvant chemotherapy for Stage III colon cancer |
| 26036466 | 2015 | RCT | BMC Cancer | Randomized Phase II study comparing S-1 dosing schedules after resection of colorectal cancer |
| 32189156 | 2020 | Clinical Study | Int J Clin Oncol | KSCC1303: S-1 + oxaliplatin (C-SOX) for Stage III colon cancer, final 3-year disease-free survival analysis |
| 25209093 | 2014 | Review | Clin Colorectal Cancer | Asian consensus guidelines for management of metastatic colorectal cancer |
| 10897209 | 2000 | Review | Gan To Kagaku Ryoho | Foundational review of S-1's biochemical modulation concept, including oteracil's role in reducing GI toxicity |
| 17496461 | 2007 | Review | Gan To Kagaku Ryoho | Status of adjuvant chemotherapy for colorectal cancer in Japan |
| 22415232 | 2012 | Clinical Study | Br J Cancer | ACTS-CC trial planned safety analysis of UFT/LV vs. S-1 as adjuvant therapy for Stage III colon cancer |
| 21875473 | 2011 | Clinical Study | Zhonghua Zhong Liu Za Zhi | Efficacy and side effects of oxaliplatin + S-1 combination therapy in postoperative colorectal cancer patients |
Finland Market Information
Oteracil-containing products (S-1 combination) are currently not marketed in Finland — no active Fimea marketing authorizations were found (0 licenses on record).
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic combination component (fluoropyrimidine-class modulator; oteracil itself has no direct cytotoxic activity — it inhibits GI-tract OPRT to reduce toxicity from tegafur-derived 5-FU) |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions |
| Emetogenicity Classification | Low to moderate (based on fluoropyrimidine class, consistent with the S-1 combination) |
| Monitoring Items | CBC with differential, liver and renal function, electrolytes |
| Handling Protection | As a component of an antineoplastic combination product, cytotoxic drug handling regulations apply |
Safety Considerations
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Three completed Phase 3 RCTs (ACTS-CC, ACTS-RC, SALTO) and multiple Phase 2 studies consistently support the efficacy of S-1 (containing oteracil) in colorectal cancer, giving this prediction L1 evidence strength. However, the product is not currently marketed in Finland and key safety/MOA data remain unavailable, so guardrails are warranted before any regulatory or clinical advancement.
To proceed, the following is needed:
- TFDA/Fimea package insert data (warnings, contraindications, drug interactions) — currently a Blocking data gap
- Detailed mechanism of action documentation for oteracil specifically (DrugBank query pending)
- Finland-specific regulatory pathway assessment, given current "not marketed" status
- Confirmation of DDI profile (current query returned "not_found")
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.