Gimeracil
| Evidence Level: L5 | Predicted Indications: 6 |
Table of Contents
Gimeracil: Cecum villous adenoma
One-Sentence Summary
Gimeracil is a component of the S-1 combination (tegafur/gimeracil/oteracil), originally used to treat gastric cancer. The clinical evidence is for the S-1 combination as a whole, not gimeracil alone.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Cecum villous adenoma |
| TxGNN Prediction Score | 0.9982 |
| Evidence Level | L5 |
| India Market Status | Listed in a compiled Indian medicine price dataset (2 of 2) – CDSCO approval status is not included in this data |
| Number of Listed Products | 2 (valid: 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 known information, gimeracil is the dihydropyrimidine dehydrogenase (DPD) inhibitor component of S-1. By inhibiting DPD, it slows the breakdown of 5-fluorouracil (5-FU, released from tegafur) and sustains 5-FU exposure.
Gastric and colorectal cancers are both gastrointestinal tumours, and 5-FU-based therapy is a standard backbone in colorectal cancer. Sustained 5-FU exposure is therefore mechanistically relevant there. Gimeracil has also reportedly inhibited homologous recombination repair, which could add chemosensitising effects, but this finding is preclinical.
An important caveat is that the benefit seen in trials belongs to the fixed-dose combination. It cannot be attributed to gimeracil independently.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00660894 | Phase 3 | Completed | 1535 | Adjuvant S-1 (TS-1) vs UFT + leucovorin in stage III colon cancer. Active-comparator design, so it informs comparative efficacy rather than superiority over placebo |
| NCT03448549 | Phase 3 | Unknown | 1191 | SOX (oxaliplatin + S-1) vs XELOX as adjuvant chemotherapy in stage III colorectal cancer. Population and endpoints should be verified |
| 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 median progression-free survival |
| NCT06255379 | Phase 2 | Not yet recruiting | 52 | Fruquintinib + tegafur/gimeracil/oteracil as third-line therapy in advanced metastatic colorectal cancer (single-arm; no outcome data yet) |
| NCT02216149 | Phase 2 | Terminated | 20 | S-1 or capecitabine with oxaliplatin, assessing coronary artery blood flow (a cardiac safety endpoint, not efficacy) |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 20811661 | 2010 | Preclinical xenograft study | Oncol Rep | Irinotecan combined with S-1 overcame 5-FU resistance in colon cancer xenografts by down-regulating thymidylate synthase |
| 20841935 | 2010 | Pharmacokinetic study | Gan To Kagaku Ryoho | Pharmacokinetics of S-1 in a mouse model of colon cancer peritoneal metastasis |
| 21084813 | 2010 | Retrospective analysis | Gan To Kagaku Ryoho | Risk factors for grade 3–4 haematological toxicity in 87 patients with advanced or recurrent colonic cancer on S-1 + irinotecan (rate 16.1%) |
| 18630468 | 2008 | Case report | Anticancer Res | Complete response maintained with S-1 + CPT-11 in colon cancer hepatic metastases |
| 29394831 | 2017 | Case report | Gan To Kagaku Ryoho | SOX + panitumumab downstaging allowed two-stage hepatectomy for unresectable colorectal liver metastases |
| 32936722 | 2021 | Case report / review | J Oncol Pharm Pract | S-1-induced hypertriglyceridaemia |
| 28414195 | 2017 | Case report | Eur J Dermatol | TS-1-induced erythroderma with extensive mucosal involvement and hand-foot syndrome |
No randomized or systematic-review literature was retrieved. The publications are preclinical studies, a retrospective analysis, and case reports, and several focus on adverse events.
India Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| Registration No. 228787 | Tegoyes 4.35mg/11.8mg/15mg Capsule (Torrent Pharmaceuticals Ltd) | Strip of 7 capsules | Not stated in the available data |
| Registration No. 226940 | Tegoyes 5.8mg/15.8mg/20mg Capsule (Torrent Pharmaceuticals Ltd) | Strip of 7 capsules | Not stated in the available data |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (fluoropyrimidine class; gimeracil is a DPD inhibitor that boosts 5-FU exposure) |
| Myelosuppression Risk | Medium. In one retrospective series with S-1 + irinotecan, grade 3–4 haematological toxicity occurred in 16.1% of patients |
| Emetogenicity Classification | Low to medium |
| Monitoring Items | CBC with differential, liver and renal function, electrolytes; watch for hand-foot syndrome, skin and mucosal reactions, and lipid abnormalities |
| Handling Protection | Follow cytotoxic drug handling regulations. Please refer to the package insert warnings and precautions |
Safety Considerations
The only safety signals available come from the retrieved literature, which describes S-1-associated adverse events:
- Hand-foot syndrome and erythroderma with mucosal involvement (case report)
- Hypertriglyceridaemia (case report)
- Grade 3–4 haematological toxicity in 16.1% of patients on S-1 + irinotecan
No data on drug interactions or knowledge-graph contraindications were found. For warnings and contraindications, please refer to the package insert.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Two Phase 3 trials, including a completed randomized trial of 1535 patients, support S-1 regimens in colon and colorectal cancer, and the mechanism (sustained 5-FU exposure via DPD inhibition) is plausible. However, the evidence applies to the S-1 combination, not gimeracil alone. The dataset has no India label text, and the other predicted indications (rank 2–10) have little or no supporting evidence.
To proceed, the following is needed:
- India package insert warnings, contraindications and approved indications (currently missing, and a blocking gap for safety screening)
- Detailed mechanism of action data
- Confirmation of outcomes from NCT00660894 and the status and results of NCT03448549
- Clarification of how the Tegoyes products (strengths and dosing) relate to the trial regimens
- A safety monitoring plan, including DPD deficiency considerations and haematological, skin and lipid monitoring
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.