Gimeracil
| Evidence Level: L1 | Predicted Indications: 10 |
Table of Contents
Using the drug-repurposing evidence pack, here is the evaluation report for Gimeracil, focused on its top-ranked predicted indication (Colonic Neoplasm), which is the only candidate with meaningful clinical/literature support (L1). The other 9 predicted indications (rank 2–10) are Hold/Research-Question stage with L4–L5 evidence and are summarized briefly at the end for completeness, per the evidence pack’s decision staging.
Gimeracil: From Gastric Cancer to Colonic Neoplasm
One-Sentence Summary
Gimeracil is the DPD-inhibitor component of the S-1 combination (tegafur + gimeracil + oteracil), a fluoropyrimidine-based regimen whose proven efficacy is in gastric cancer. The TxGNN model predicts it may also be effective for Colonic Neoplasm (colorectal cancer), with 8 clinical trials and 15 publications currently supporting this direction — though the clinical evidence is attributable to the S-1 combination as a whole, not to Gimeracil as a standalone agent, and Gimeracil is not currently marketed in Taiwan.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Gastric cancer (as a component of the S-1 combination; not individually registered in Taiwan) |
| Predicted New Indication | Colonic Neoplasm (Colorectal Cancer) |
| TxGNN Prediction Score | 99.88% |
| Evidence Level | L1 |
| Taiwan Market Status | Not marketed (Not Marketed) |
| Number of Registrations | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data for Gimeracil alone is not available (Data Gap). Based on known information, Gimeracil is part of the S-1 combination (tegafur/gimeracil/oteracil), where it functions as a dihydropyrimidine dehydrogenase (DPD) inhibitor. By blocking DPD-mediated breakdown of 5-fluorouracil (the active metabolite of tegafur), Gimeracil raises and sustains intratumoral 5-FU concentrations, and its efficacy as part of S-1 in gastric cancer has been proven in multiple regulatory jurisdictions.
Gastric cancer and colonic neoplasm are both gastrointestinal adenocarcinomas that respond to fluoropyrimidine-based chemotherapy through the same core mechanism — thymidylate synthase inhibition potentiated by DPD blockade. This mechanistic overlap is precisely why S-1 has already been separately approved and extensively trialed for colorectal cancer in multiple countries (including large Phase 3 adjuvant and metastatic trials), independent of the TxGNN prediction.
The caveat is that the supporting clinical evidence below is generated with the S-1 combination product, not Gimeracil in isolation. Since Gimeracil is not marketed as a standalone drug in Taiwan and has no local approval record, any repurposing pathway would need to proceed via the combination product or with explicit bridging justification for the single component.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01918852 | Phase 3 | Completed | 161 | SALTO trial — randomized S-1 vs. capecitabine (± bevacizumab) as first-line therapy for metastatic colorectal cancer; direct head-to-head efficacy/safety evidence for S-1 (Grade A relevance). |
| NCT00660894 | Phase 3 | Completed | 1535 | Large adjuvant RCT comparing UFT+leucovorin vs. TS-1 (S-1) in Stage III colon cancer, with gene-expression predictive-factor analysis (Grade A relevance). |
| NCT03448549 | Phase 3 | Unknown | 1191 | SOX (S-1+oxaliplatin) vs. XELOX as adjuvant chemotherapy for Stage III colorectal cancer; large sample size but results not yet publicly reported. |
| NCT02618356 | Phase 2 | Unknown | 82 | Raltitrexed + S-1 for metastatic colorectal cancer after failure of standard chemotherapy; primary endpoint was progression-free survival. |
| NCT00974389 | Phase 2 | Unknown | 40 | S-1 + bevacizumab in unresectable/recurrent colorectal cancer after prior irinotecan/oxaliplatin failure. |
| NCT00524706 | Phase 1/2 | Unknown | 42 | S-1 + oral leucovorin + oxaliplatin (SOL regimen) in untreated metastatic colorectal cancer; early-phase activity/toxicity data. |
| NCT02216149 | Phase 2 | Terminated | 20 | Evaluated cardiac microvascular safety of S-1/capecitabine + oxaliplatin in metastatic GI adenocarcinoma; not an efficacy trial, low relevance. |
| NCT06255379 | Phase 2 | Not yet recruiting | 52 | Planned trial of fruquintinib + S-1 as third-line therapy for advanced metastatic CRC; no data available yet. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 41724114 | 2026 | Real-world cohort | European Journal of Cancer | Population-based study of S-1 safety/feasibility as adjuvant therapy after capecitabine-induced hand-foot syndrome or cardiotoxicity in colon cancer. |
| 21084813 | 2010 | Cohort | Gan To Kagaku Ryoho | Risk-factor analysis for Grade 3–4 hematologic toxicity in 87 patients receiving S-1 + irinotecan for advanced/recurrent colonic cancer (16.1% severe toxicity rate). |
| 21875473 | 2011 | Cohort | Zhonghua Zhong Liu Za Zhi | Efficacy and adverse-effect profile of oxaliplatin + S-1 in postoperative colorectal cancer patients. |
| 20841935 | 2010 | Cohort/PK 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 overcomes 5-FU resistance in colon cancer xenografts via S-1-mediated thymidylate synthase down-regulation. |
| 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 | Two-stage hepatectomy following SOX (S-1+oxaliplatin) + panitumumab downstaging for irresectable colorectal liver metastases. |
| 29483452 | 2018 | Case Report | Gan To Kagaku Ryoho | Transverse colon cancer with liver metastasis and portal vein tumor thrombosis effectively treated with combination chemotherapy including S-1-based regimens. |
| 32936722 | 2021 | Case Report | J Oncol Pharm Practice | Hypertriglyceridemia induced by S-1 in a colorectal cancer patient — a distinct safety signal. |
| 28414195 | 2017 | Case Report | Eur J Dermatol | TS-1 (tegafur/gimeracil/oteracil)-induced erythroderma with extensive mucosal involvement and hand-foot syndrome. |
Taiwan Market Information
Gimeracil currently has no marketing authorization in Taiwan (market_status: Not marketed, 0 registrations, no license records available). No approved product, dosage form, or labeled indication exists locally for this drug as a standalone entity or within an S-1 combination product.
Cytotoxicity
Gimeracil, as the DPD-inhibitor component of the cytotoxic fluoropyrimidine combination S-1, is classified as an antineoplastic agent.
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (fluoropyrimidine-potentiating agent; DPD inhibitor component of the S-1 regimen) |
| Myelosuppression Risk | Moderate — literature reports a 16.1% rate of Grade 3–4 hematologic toxicity with S-1 + irinotecan in colonic cancer patients (PMID 21084813) |
| Emetogenicity Classification | Low to moderate (consistent with fluoropyrimidine-class regimens) |
| Monitoring Items | CBC with differential, liver and renal function, serum triglycerides (per reported hypertriglyceridemia signal), skin/mucosal assessment (per reported erythroderma and hand-foot syndrome) |
| Handling Protection | Standard cytotoxic drug handling precautions apply, as Gimeracil is administered only as part of a cytotoxic combination regimen |
Safety Considerations
No formal drug label warnings, contraindications, or drug-drug interaction data are currently available for Gimeracil (label review and DDI database queries returned no results). Please refer to the package insert for official safety information.
Adverse events reported in the literature (not formal label warnings, but noted for awareness):
- Hypertriglyceridemia associated with S-1 administration (PMID 32936722)
- Erythroderma with extensive mucosal involvement and hand-foot syndrome (PMID 28414195)
- Grade 3–4 hematologic toxicity in 16.1% of patients receiving S-1 + irinotecan (PMID 21084813)
Other Predicted Indications (Lower Priority)
The remaining 9 TxGNN-predicted indications for Gimeracil all fall at L4–L5 evidence levels with Hold or Research Question status, and are not recommended for near-term action:
- Cardia cancer (L4, Research Question) — mechanistically plausible (gastric adenocarcinoma subtype) but supported only by a single case report.
- Rectosigmoid junction neoplasm (L5, Research Question) — anatomically/histologically adjacent to colonic neoplasm; no direct trial or literature evidence yet.
- Cecum villous adenoma, malignant gastric granular cell tumor, lipoma of colon, cecum neuroendocrine tumor G1, colonic lymphangioma, colon leiomyoma, gastric lymphoma (all L5, Hold) — benign, non-chemotherapy-responsive, or mechanistically unrelated conditions with no supporting clinical trial or literature evidence; likely low-specificity artifacts of the knowledge graph.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Multiple Phase 3 RCTs (including two large, completed trials: SALTO, n=161, and the UFT+LV vs. TS-1 adjuvant trial, n=1535) directly support the efficacy of the S-1 combination — which contains Gimeracil — in colorectal cancer. However, this evidence is attributable to the combination product, not Gimeracil as a standalone agent, and Gimeracil has no market authorization or safety labeling in Taiwan.
To proceed, the following is needed:
- TFDA-approved package insert data (warnings, contraindications) — currently a Blocking data gap
- Formal mechanism-of-action documentation for Gimeracil specifically (via DrugBank or manufacturer data) — currently a High-severity data gap
- Clarification on whether the repurposing pathway targets Gimeracil alone or the full S-1 combination product, since all supporting clinical evidence is combination-based
- A regulatory strategy given the drug’s current unmarketed status in Taiwan
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.