Capecitabine
| Evidence Level: L1 | Predicted Indications: 10 |
Table of Contents
Capecitabine: From Gastric Cancer to Gastric Tubular Adenocarcinoma
One-Sentence Summary
Capecitabine is an oral fluoropyrimidine chemotherapy originally used for colon cancer metastases and gastric cancer. The TxGNN model predicts it may be effective for gastric tubular adenocarcinoma (the top-ranked prediction with supporting evidence), with 0 registered clinical trials and 20 publications, including multiple Phase 3 RCTs, currently supporting this direction. Most of this evidence covers the broad gastric/gastroesophageal junction (GEJ) adenocarcinoma population, so this is largely an extension within the existing gastric cancer indication rather than a true repurposing.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Metastasis from malignant tumour of colon; gastric cancer (the Singapore licence records contain no approved indication text) |
| Predicted New Indication | Gastric tubular adenocarcinoma (the rank 1 prediction, gastric adenocarcinoma and proximal polyposis of the stomach, has no supporting evidence and is on hold) |
| TxGNN Prediction Score | 99.94% |
| Evidence Level | L1 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 10 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, capecitabine is an oral prodrug of 5-fluorouracil (5-FU). It is converted to 5-FU, which inhibits thymidylate synthase and damages DNA and RNA. It is an established backbone of gastric cancer chemotherapy.
Tubular adenocarcinoma is a common histologic subtype of gastric adenocarcinoma. Because capecitabine is already used for gastric cancer, this prediction falls largely within the existing indication. The mechanism of 5-FU-based cytotoxicity does not depend on this specific subtype.
Other predictions in the list, for context:
- Gastric cardia adenocarcinoma (rank 5): Level L2 evidence, with three completed trials of capecitabine regimens. Proceed with Guardrails.
- Signet ring cell gastric adenocarcinoma (rank 4), gastric body carcinoma (rank 8), carcinoma of stomach salivary gland type (rank 7), EBV-associated gastric carcinoma (rank 9): Evidence is mixed-population, early-phase, or confounded by combination agents. Research questions.
- Proximal polyposis syndrome (rank 1), microinvasive gastric cancer (rank 3), gastric pylorus carcinoma (rank 6), malignant gastric granular cell tumour (rank 10): Little or no supporting evidence. Hold. Microinvasive disease is usually treated by resection, and granular cell tumours are not epithelial adenocarcinomas.
Clinical Trial Evidence
No clinical trials are registered specifically for gastric tubular adenocarcinoma. Currently no related clinical trials registered for this indication.
For reference, the trials retrieved for the closely related gastric cardia adenocarcinoma prediction (rank 5) are:
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00040859 | Phase 2 | Completed | 48 | Oxaliplatin + capecitabine in metastatic oesophageal, GEJ and gastric cardia adenocarcinoma |
| NCT00938470 | Phase 2 | Completed | 73 | Randomised extended neoadjuvant therapy in locally advanced oesophageal, GEJ and gastric cardia adenocarcinoma; capecitabine is part of a combination |
| NCT01295086 | N/A | Completed | 27 | Dose-finding of docetaxel/oxaliplatin/capecitabine with trastuzumab in HER2-positive oesophagus, cardia or gastric cancer |
Literature Evidence
Evidence for gastric tubular adenocarcinoma (the 10 most relevant publications, RCTs first):
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 22226517 | 2012 | RCT (Phase 3) | Lancet | CLASSIC: adjuvant capecitabine + oxaliplatin after D2 gastrectomy vs surgery alone in stage II-IIIB gastric cancer |
| 20728210 | 2010 | RCT (Phase 3) | Lancet | ToGA: trastuzumab plus chemotherapy vs chemotherapy alone in HER2-positive advanced gastric/GEJ cancer |
| 34252374 | 2021 | RCT (Phase 3) | Lancet Oncol | RESOLVE: perioperative/postoperative SOX vs adjuvant CapOx after D2 gastrectomy |
| 39952264 | 2025 | RCT (Phase 3) | Lancet Oncol | RESOLVE final report with updated survival data |
| 30982686 | 2019 | RCT (Phase 2/3) | Lancet | FLOT4: perioperative FLOT vs ECF/ECX in resectable gastric/GEJ adenocarcinoma |
| 37524953 | 2023 | RCT (Phase 3) | Nat Med | GLOW: zolbetuximab + CAPOX in CLDN18.2-positive gastric/GEJ adenocarcinoma |
| 34102137 | 2021 | RCT (Phase 3) | Lancet | CheckMate 649: first-line nivolumab + chemotherapy vs chemotherapy alone |
| 37875143 | 2023 | RCT (Phase 3) | Lancet Oncol | KEYNOTE-859: pembrolizumab + chemotherapy in HER2-negative advanced gastric cancer |
| 38806195 | 2024 | RCT (Phase 3) | BMJ | RATIONALE-305: tislelizumab + chemotherapy as first-line treatment |
| 38051328 | 2023 | RCT (Phase 3) | JAMA | ORIENT-16: sintilimab + chemotherapy in unresectable gastric/GEJ cancer |
Further Phase 3 trials (sugemalimab, GEMSTONE-303; adjuvant nivolumab, ATTRACTION-5) and several Phase 2 studies are also available. Of these, CLASSIC and RESOLVE evaluated capecitabine-based regimens directly. In the immunotherapy and targeted-agent trials, capecitabine is part of the chemotherapy backbone, so its individual contribution cannot be isolated.
Singapore Market Information
Capecitabine has 10 valid single-ingredient registrations in Singapore (no cancelled licences). Approved indication text is not recorded for any of them.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN10677P | XELODA Tablets 500 mg | Film-coated tablet | Not recorded |
| SIN10678P | XELODA Tablets 150 mg | Film-coated tablet | Not recorded |
| SIN15464P | INTACAPE Film Coated Tablet 500 mg | Film-coated tablet | Not recorded |
| SIN15463P | INTACAPE Film Coated Tablet 150 mg | Film-coated tablet | Not recorded |
| SIN14799P | CAPETERO Capecitabine Tablets 500 mg | Tablet | Not recorded |
Other registrations: KAPETRAL (150 mg and 500 mg) and INCITABINE (150 mg and 500 mg), plus CAPETERO 150 mg (SIN14798P).
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (fluoropyrimidine class, oral 5-FU prodrug) |
| Myelosuppression Risk | Medium (the knowledge graph links capecitabine to neutropenia, thrombocytopenia, anaemia and agranulocytosis as contraindicated conditions) |
| Emetogenicity Classification | Low to moderate |
| Monitoring Items | CBC with differential, liver function (including bilirubin), renal function |
| Handling Protection | Follow cytotoxic drug handling regulations; please refer to the package insert warnings and precautions |
Safety Considerations
Package insert warnings and contraindications were not available in the data compiled for this report. Please refer to the package insert for authoritative safety information.
- Contraindication-related conditions (from a knowledge graph, not label text): liver disease, gallbladder disease, thrombocytopenia, neutropenia, agranulocytosis, anaemia, hyperbilirubinaemia (including Gilbert syndrome), impaired renal function, coronary artery disease, sudden cardiac arrest, heart conduction disease, infectious disease, stomatitis, necrotising enterocolitis, and dihydropyrimidine dehydrogenase (DPD) deficiency. DPD deficiency screening is particularly relevant for fluoropyrimidines.
- Drug Interactions: 100 interactions were found. The main moderate-level ones are metronidazole and tinidazole. Minor ones include levofloxacin and antacids (aluminium hydroxide, magaldrate, magnesium carbonate/hydroxide/oxide). Others, such as proton pump inhibitors, metformin, simvastatin and morphine, have unclassified severity.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Multiple Phase 3 RCTs, including CLASSIC and RESOLVE, support capecitabine-based chemotherapy in gastric adenocarcinoma, and capecitabine is already an established part of gastric cancer treatment. This is an extension within the existing indication rather than true repurposing. The evidence is not specific to the tubular subtype, and many trials use combination regimens.
To proceed, the following is needed:
- Package insert warnings and contraindications (a blocking gap for safety screening), from the HSA website
- Mechanism of action data from DrugBank
- Approved indication text for the Singapore licences, to confirm gastric cancer coverage
- DPD deficiency screening and biomarker selection (HER2, PD-L1, CLDN18.2) where applicable
- Subtype-specific analysis of the existing trials for tubular adenocarcinoma
- Hold the predictions with no evidence (proximal polyposis syndrome, microinvasive gastric cancer, malignant gastric granular cell tumour) until supporting data emerge
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.