Gimeracil
| Evidence Level: L1 | Predicted Indications: 10 |
Table of Contents
Gimeracil: From Gastric Cancer to Colonic Neoplasm
One-Sentence Summary
Gimeracil is a component of the S-1 combination (tegafur/gimeracil/oteracil), originally used to treat gastric cancer. The TxGNN model predicts it may be effective for colonic neoplasm, with 6 clinical trials and 12 publications currently supporting this direction. Note that this evidence applies to the S-1 combination, not gimeracil alone.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Gastric cancer (the Singapore licence records contain no approved indication text) |
| Predicted New Indication | Colonic neoplasm |
| TxGNN Prediction Score | 99.88% |
| 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 in the data compiled for this report. Based on general pharmacology knowledge, gimeracil is part of S-1 (tegafur + gimeracil + oteracil). It inhibits the enzyme dihydropyrimidine dehydrogenase (DPD), which slows the breakdown of 5-FU and raises and prolongs systemic 5-FU exposure from tegafur. Gimeracil has no standalone antitumour activity.
Gastric cancer and colorectal cancer are both gastrointestinal tumours, and colorectal cancer is sensitive to 5-FU. The mechanism therefore links directly to the original gastric cancer indication. This supports the reasonableness of the TxGNN prediction, but any benefit would come from the S-1 combination as a whole.
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; directly tests S-1 |
| NCT03448549 | Phase 3 | Unknown | 1191 | SOX (oxaliplatin + S-1) vs XELOX as adjuvant chemotherapy for stage III colorectal cancer; no results available |
| NCT00974389 | Phase 2 | Unknown | 40 | S-1 + bevacizumab in unresectable or recurrent colorectal cancer after failure of prior chemotherapy |
| 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 | Fruquintinib + tegafur/gimeracil/oteracil as third-line treatment in advanced metastatic colorectal cancer |
| NCT02216149 | Phase 2 | Terminated | 20 | S-1 vs capecitabine with oxaliplatin on coronary artery blood flow; a safety endpoint, not efficacy |
Literature Evidence
No randomised trials or systematic reviews were identified. The available literature consists mainly of case reports, plus preclinical and pharmacokinetic studies.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 20841935 | 2010 | Pharmacokinetic study | Gan to Kagaku Ryoho | Pharmacokinetics of S-1 in a mouse model of peritoneal metastasis from colon cancer |
| 20811661 | 2010 | Preclinical (xenograft) | Oncology Reports | Irinotecan combined with S-1 enhanced antitumour activity in 5-FU-resistant colon cancer xenografts by down-regulating thymidylate synthase |
| 21084813 | 2010 | Clinical analysis | Gan to Kagaku Ryoho | Risk factors for grade 3-4 haematological toxicity in 87 patients receiving S-1 + irinotecan for advanced or recurrent colonic cancer (rate 16.1%) |
| 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 as downstaging chemotherapy enabling two-stage hepatectomy for colorectal liver metastases |
| 32936722 | 2021 | Case report | J Oncol Pharm Pract | Hypertriglyceridaemia induced by S-1 |
| 28414195 | 2017 | Case report | Eur J Dermatol | TS-1-induced erythroderma with extensive mucosal involvement and hand-foot syndrome |
| 41253353 | 2025 | Case report | Gan to Kagaku Ryoho | Urinary retention from oxaliplatin-induced acute peripheral neuropathy in a patient previously treated with tegafur/gimeracil/oteracil |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN13672P | TS-ONE Capsule 20 | Capsule | Not stated in the available licence record |
| SIN13673P | TS-ONE Capsule 25 | Capsule | Not stated in the available licence record |
Both licences are valid single-ingredient registrations held by Taiho Pharmaceutical Co., Ltd. (Tokushima Plant), for oral use.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (fluoropyrimidine class; gimeracil acts as a DPD inhibitor within the S-1 combination) |
| Myelosuppression Risk | Medium (one study reported grade 3-4 haematological toxicity in 16.1% of patients receiving S-1 + irinotecan) |
| Emetogenicity Classification | Low to moderate |
| Monitoring Items | CBC (with differential), liver and renal function, electrolytes |
| Handling Protection | Follow cytotoxic drug handling regulations |
Safety Considerations
Please refer to the package insert for safety information. No drug interactions were found in the queried database, and no knowledge-graph contraindications were recorded.
Adverse events reported in the literature for S-1-containing regimens include hand-foot syndrome, erythroderma with mucosal involvement, hypertriglyceridaemia and haematological toxicity.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: One completed Phase 3 trial (NCT00660894, n=1535) tests S-1 directly in stage III colon cancer, and a further Phase 3 trial and several Phase 2 trials are registered. The strongest evidence level (L1) is nominal: only one of the Phase 3 trials is completed, and the other has an unknown status with no results. The evidence also concerns the S-1 combination, not gimeracil alone, so any decision must be made at the combination level.
To proceed, the following is needed:
- Package insert warnings and contraindications from the HSA (currently missing, and blocking safety screening)
- Mechanism of action data from DrugBank
- Published results of the completed Phase 3 trial (NCT00660894) and the SOX trial (NCT03448549)
- The approved indication text for the Singapore licences, to confirm the original indication
- A safety monitoring plan covering haematological toxicity, hand-foot syndrome and DPD-related risks
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.