Oteracil
| Evidence Level: L1 | Predicted Indications: 10 |
Table of Contents
Oteracil: From Gastric Cancer to Colonic Neoplasm
One-Sentence Summary
Oteracil is a component of the S-1 combination (tegafur/gimeracil/oteracil), originally used for gastric cancer treatment. The TxGNN model predicts it may be effective for Colonic Neoplasm, with 6 clinical trials and 10 publications currently supporting this direction. The evidence applies to S-1 as a combination, not to oteracil as a standalone agent.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Gastric cancer (the licence records contain no approved indication text; this comes from the knowledge-graph indication data) |
| Predicted New Indication | Colonic neoplasm |
| TxGNN Prediction Score | 99.99% |
| Evidence Level | L1 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 2 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available from the source records. Based on general pharmacology, oteracil is one of three components of S-1 (tegafur + gimeracil + oteracil). It is not an antitumour agent by itself. Tegafur, a 5-FU prodrug, provides the antitumour activity. Oteracil inhibits orotate phosphoribosyltransferase (OPRT) in the gastrointestinal mucosa, which reduces local activation of 5-FU and therefore its gastrointestinal toxicity.
Gastric cancer and colonic neoplasm are both gastrointestinal tumours that respond to fluoropyrimidine therapy. Several trials of S-1 regimens in colorectal cancer, including two Phase 3 trials, are consistent with the model's prediction.
The very high TxGNN score likely reflects the drug's association with fluoropyrimidine-treated gastrointestinal cancers. The evidence supports S-1 as a combination product, not oteracil alone.
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 |
| NCT03448549 | Phase 3 | Unknown | 1191 | SOX (oxaliplatin + S-1) vs XELOX as adjuvant chemotherapy for stage III colorectal cancer; aims to reduce hand-foot syndrome seen with capecitabine |
| NCT00974389 | Phase 2 | Unknown | 40 | S-1 + bevacizumab in unresectable or recurrent colorectal cancer after prior chemotherapy failure |
| NCT02618356 | Phase 2 | Unknown | 82 | Raltitrexed + S-1 in metastatic colorectal cancer after standard chemotherapy failure; primary endpoint is progression-free survival |
| NCT06255379 | Phase 2 | Not yet recruiting | 52 | Single-arm study of fruquintinib + tegafur/gimeracil/oteracil as third-line treatment of advanced metastatic colorectal cancer |
| NCT02216149 | Phase 2 | Terminated | 20 | Cardiac safety study (coronary blood flow) of S-1 vs capecitabine with oxaliplatin; not an efficacy study |
Literature Evidence
The retrieved literature consists mainly of case reports and one preclinical study. No randomised trials were retrieved.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 21084813 | 2010 | Retrospective cohort | Gan To Kagaku Ryoho | Risk factors for grade 3-4 haematological toxicity (16.1%) in 87 patients with advanced or recurrent colonic cancer receiving S-1 + irinotecan |
| 20811661 | 2010 | Preclinical (xenograft) | Oncology Reports | Irinotecan combined with S-1 augmented antitumour activity in 5-FU-resistant human colon cancer xenografts |
| 18630468 | 2008 | Case report | Anticancer Research | Complete response maintained with S-1 + CPT-11 in hepatic metastases of colon cancer |
| 29394831 | 2017 | Case report | Gan To Kagaku Ryoho | SOX plus panitumumab downstaged unresectable colorectal liver metastases, allowing two-stage hepatectomy |
| 32936722 | 2021 | Case report (adverse event) | J Oncol Pharm Pract | Hypertriglyceridaemia induced by S-1 in a colorectal cancer patient, with literature review |
| 28414195 | 2017 | Case report (adverse event) | Eur J Dermatol | TS-1-induced erythroderma with extensive mucosal involvement and hand-foot syndrome |
| 41253353 | 2025 | Case report (adverse event) | Gan To Kagaku Ryoho | Urinary retention from oxaliplatin-induced acute peripheral neuropathy in a patient previously treated with tegafur/gimeracil/oteracil |
| 35444144 | 2022 | Case report | Gan To Kagaku Ryoho | Repeated laparoscopic resection of peritoneal recurrences after colorectal cancer resection |
| 30692384 | 2018 | Case report | Gan To Kagaku Ryoho | CT-guided celiac plexus neurolysis for pain from postoperative recurrence of colon cancer, after oral adjuvant chemotherapy |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN13672P | TS-ONE Capsule 20 | Capsule | Not recorded in the compiled data |
| SIN13673P | TS-ONE Capsule 25 | Capsule | Not recorded in the compiled data |
Both licences are valid, single-ingredient registrations held by Taiho Pharmaceutical Co., Ltd. (Tokushima Plant). Both products are oral capsules.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (fluoropyrimidine class; oteracil is a modulating component of S-1) |
| Myelosuppression Risk | Moderate; one retrospective study of S-1 + irinotecan found grade 3-4 haematological toxicity in 16.1% of patients |
| Emetogenicity Classification | Low to moderate (general class estimate) |
| Monitoring Items | CBC with differential, liver and renal function, electrolytes |
| Handling Protection | Follow cytotoxic drug handling regulations |
Reported adverse events with S-1 regimens include hand-foot syndrome, erythroderma with mucosal involvement and hypertriglyceridaemia (case reports).
Safety Considerations
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Two Phase 3 trials, one of them completed with 1535 patients, test S-1 regimens in colon and colorectal cancer. However, the evidence concerns the S-1 combination, not oteracil alone, and the literature is mostly case reports. The other predicted indications (benign or non-specific colonic conditions) have no supporting evidence and should stay on hold.
To proceed, the following is needed:
- Package insert warnings and contraindications from the HSA, which are currently missing and block safety screening
- Mechanism of action data confirmed from DrugBank
- Published results of the completed Phase 3 trial (NCT00660894) and of the Phase 3 SOX trial (NCT03448549), whose status is unknown
- Confirmation of the approved indications on the Singapore TS-ONE licences, to establish whether colorectal cancer is covered
- A safety monitoring plan, including haematological and skin toxicity surveillance
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.