Gimeracil

證據等級: L5

預測適應症: 10 個

Gimeracil: From Gastric Cancer to Colonic Neoplasm

One-Sentence Summary

Gimeracil is a component of the S-1 fixed-dose combination (tegafur/gimeracil/oteracil), a DPD (dihydropyrimidine dehydrogenase) inhibitor that potentiates 5-FU activity, with proven efficacy in gastric cancer. The TxGNN model predicts it may be effective for Colonic Neoplasm, with 8 clinical trials and 15 publications currently supporting this direction, including two completed Phase 3 RCTs.

Quick Overview

Item	Content
Original Indication	Gastric Cancer (as part of the S-1 combination; no standalone Taiwan/Finland regulatory record on file)
Predicted New Indication	Colonic Neoplasm
TxGNN Prediction Score	99.88%
Evidence Level	L1
Finland Market Status	未上市 (Not Marketed)
Number of Authorizations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data for gimeracil is not available (data gap). Based on known information, gimeracil is not itself cytotoxic — it is the DPD-inhibitor component of the S-1 fixed-dose combination (tegafur + gimeracil + oteracil). By blocking DPD-mediated breakdown of the 5-FU generated from tegafur, gimeracil raises and sustains intratumoral 5-FU concentrations, enhancing the combination's antitumour activity. S-1's efficacy in gastric cancer has been proven and forms the pharmacological basis for extrapolation to colonic neoplasm.

Gastric cancer and colonic neoplasm are both gastrointestinal, fluoropyrimidine-sensitive tumours sharing the same 5-FU-driven mechanism of action. S-1-based regimens (SOX, S-1+irinotecan, S-1+leucovorin) are already established chemotherapy backbones in colorectal cancer across multiple Asian and European trials, which supports the biological plausibility of the TxGNN prediction.

It is important to note that any observed efficacy is attributable to the S-1 combination as a whole, not to gimeracil as a standalone agent — gimeracil has no independent antitumour activity and functions purely as a pharmacokinetic enhancer within the fixed-dose product.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT01918852	Phase 3	Completed	161	SALTO study: S-1 vs. capecitabine (± bevacizumab) as first-line treatment for metastatic colorectal cancer
NCT00660894	Phase 3	Completed	1535	UFT+leucovorin vs. TS-1 (contains gimeracil) as adjuvant treatment for Stage III colon cancer, with gene-expression predictive factor analysis
NCT03448549	Phase 3	Unknown	1191	SOX (S-1+oxaliplatin) vs. XELOX as adjuvant chemotherapy for Stage III colorectal cancer
NCT02618356	Phase 2	Unknown	82	Raltitrexed + S-1 in metastatic colorectal cancer after failure of standard chemotherapy
NCT00524706	Phase 1/2	Unknown	42	S-1 + oral leucovorin + oxaliplatin (SOL regimen) in untreated metastatic colorectal cancer
NCT00974389	Phase 2	Unknown	40	S-1 + bevacizumab in unresectable/recurrent colorectal cancer after prior irinotecan/oxaliplatin failure
NCT02216149	Phase 2	Terminated	20	S-1 vs. capecitabine + oxaliplatin: comparison of subclinical coronary microvascular toxicity in metastatic GI adenocarcinoma
NCT06255379	Phase 2	Not yet recruiting	52	Fuquinitinib + tegafur/gimeracil/oteracil as third-line treatment for advanced metastatic colorectal cancer

Literature Evidence

PMID	Year	Type	Journal	Key Findings
41724114	2026	Real-world Study	Eur J Cancer	Population-based study: S-1 is feasible after capecitabine-induced hand-foot syndrome/cardiotoxicity in adjuvant colon cancer treatment
21875473	2011	Cohort/Clinical Study	Zhonghua Zhong Liu Za Zhi	Efficacy and side effects of oxaliplatin + S-1 combination in postoperative colorectal cancer patients
21084813	2010	Cohort (Safety)	Gan To Kagaku Ryoho	Risk factors for severe (grade 3-4) hematological toxicity (16.1% incidence) with S-1 + irinotecan in advanced/recurrent colonic cancer
20841935	2010	Pharmacokinetic Study	Gan To Kagaku Ryoho	Pharmacokinetics of S-1 for treatment of peritoneal metastasis in a mouse colon cancer model
20811661	2010	Preclinical (Xenograft)	Oncology Reports	Irinotecan overcomes 5-FU resistance in colon cancer xenografts via downregulation of thymidylate synthase, combined with oral S-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	Two-stage hepatectomy after SOX (S-1+oxaliplatin) + panitumumab downstaging for irresectable colorectal liver metastases
32936722	2021	Case Report	J Oncol Pharm Pract	Hypertriglyceridemia induced by S-1 in a colorectal cancer patient
28414195	2017	Case Report	Eur J Dermatol	S-1-induced erythroderma with extensive mucosal involvement and hand-foot syndrome
35444144	2022	Case Report	Gan To Kagaku Ryoho	Laparoscopic resection of peritoneal recurrences after colorectal cancer surgery

Cytotoxicity

Item	Content
Cytotoxicity Classification	Conventional cytotoxic (fluoropyrimidine-class combination) — gimeracil itself is a non-cytotoxic DPD inhibitor that potentiates 5-FU cytotoxicity within the S-1 product
Myelosuppression Risk	Medium — grade 3-4 hematological toxicity reported in ~16.1% of patients receiving S-1 + irinotecan (PMID 21084813)
Emetogenicity Classification	Low to Moderate (depends on combination partner; higher when combined with oxaliplatin/irinotecan)
Monitoring Items	CBC with differential, renal function (dose adjustment required per renal clearance), hepatic function, triglycerides (reported hypertriglyceridemia), skin/mucosal toxicity
Handling Protection	Standard cytotoxic drug handling precautions apply, consistent with fluoropyrimidine chemotherapy agents

Safety Considerations

Please refer to the package insert for safety information.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: Two completed Phase 3 RCTs (SALTO, NCT01918852, n=161; NCT00660894, n=1535) directly support the efficacy of S-1 — the fixed-dose combination containing gimeracil — in colorectal/colon cancer, meeting the L1 evidence-level threshold. However, gimeracil's contribution is only demonstrable as part of the S-1 combination, not as a standalone agent, and critical safety/regulatory data (TFDA/Finland package insert, MOA detail) remain unavailable.

To proceed, the following is needed:

TFDA/Finland package insert warnings, contraindications, and precautions (DG001, Blocking gap)
Detailed mechanism of action data from DrugBank (DG002, High priority)
Drug interaction (DDI) data, currently not found in the source database
Clarification of whether the repurposing claim applies to gimeracil alone or requires the full S-1 combination
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.