Irinotecan
| Evidence Level: L3 | Predicted Indications: 10 |
Table of Contents
- Irinotecan
- Irinotecan: From Metastatic Colon Cancer and Pancreatic Adenocarcinoma to Female Breast Carcinoma
Irinotecan: From Metastatic Colon Cancer and Pancreatic Adenocarcinoma to Female Breast Carcinoma
One-Sentence Summary
Irinotecan is a topoisomerase I inhibitor originally used for metastatic colon cancer and pancreatic adenocarcinoma. The TxGNN model predicts it may be effective for female breast carcinoma, but the direct evidence is thin: 9 clinical trials (only 1 directly in breast cancer, and that is a small Phase 1 study) and 20 publications, most of which concern sacituzumab govitecan, not irinotecan itself.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Metastatic colon cancer; pancreatic adenocarcinoma (from the knowledge graph; no approved-indication text is available in the Singapore licence records) |
| Predicted New Indication | Female breast carcinoma |
| TxGNN Prediction Score | 99.08% |
| Evidence Level | L3 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 11 |
| Recommended Decision | Hold (treat as a research question) |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on the published literature, irinotecan is a prodrug of SN-38, which inhibits topoisomerase I and causes double-strand DNA breaks in dividing cells. Its efficacy in colorectal and pancreatic cancer is established.
The strongest mechanistic support comes from sacituzumab govitecan, a Trop-2 antibody-drug conjugate that carries SN-38 as its payload. It is approved for metastatic triple-negative breast cancer, and a Phase III study (TROPiCS-02) examined it in HR+/HER2- disease. This suggests topoisomerase I inhibition is a valid mechanism in breast cancer. However, that evidence concerns the conjugate, not irinotecan itself. Direct irinotecan evidence consists of small Phase 1 combination studies and a Phase 2 study of liposomal irinotecan in HER2-negative breast cancer with brain metastases (PHENOMENAL, 2026), whose results are not detailed in the data compiled.
Clinical Trial Evidence
Only trials with direct or partial relevance are listed first. Most of the others are studies of other investigational drugs in which irinotecan is a possible combination partner.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00083148 | Phase 1 | Completed | 12 | Irinotecan followed by capecitabine in advanced breast carcinoma; directly relevant but small and early-phase |
| NCT00031681 | Phase 1 | Completed | 41 | UCN-01 plus irinotecan in resistant solid tumours, with a triple-negative breast cancer cohort |
| NCT00004095 | Phase 1 | Completed | 38 | Irinotecan plus gemcitabine in solid tumours; not breast-specific |
| NCT05453825 | Phase 2 | Unknown | 180 | Navicixizumab alone or with paclitaxel or irinotecan; includes a triple-negative breast cancer cohort; relevance of irinotecan unclear |
| NCT03678883 | Phase 2 | Active, not recruiting | 350 | 9-ING-41 (GSK-3β inhibitor) alone or with chemotherapy in refractory cancers; focus is the investigational agent |
| NCT02419495 | Phase 1 | Terminated | 221 | Selinexor with several standard chemotherapies; irinotecan is one backbone |
| NCT06840886 | Phase 1 | Recruiting | 426 | First-in-human study of PHST001 in solid tumours; irinotecan at most a partner |
| NCT06769425 | Phase 1 | Recruiting | 157 | PARP1 inhibitor HS-10502 combinations in solid tumours; indirect relevance |
| NCT05238831 | Early Phase 1 | Withdrawn | 0 | Precision-medicine pilot (SMMART-ACT); no participants, no usable evidence |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 32223649 | 2020 | RCT (design paper) | Future Oncol | TROPiCS-02: Phase III of sacituzumab govitecan (SN-38 payload) in HR+/HER2- metastatic breast cancer |
| 23168366 | 2013 | RCT | Lancet Oncol | Continuing bevacizumab after progression in metastatic colorectal cancer (not breast) |
| 41371050 | 2026 | Phase 2 | Eur J Cancer | PHENOMENAL: liposomal irinotecan in HER2-negative breast cancer with brain metastases |
| 28291390 | 2017 | Single-arm trial | J Clin Oncol | Sacituzumab govitecan in heavily pretreated metastatic triple-negative breast cancer |
| 25944802 | 2015 | Phase 1 | Clin Cancer Res | First-in-human trial of sacituzumab govitecan in diverse metastatic solid tumours |
| 12800602 | 2003 | Review | Oncology (Williston Park) | Rationale for mitomycin plus irinotecan in advanced breast cancer; marginal single-agent activity but preclinical synergy |
| 9726101 | 1998 | Review | Oncology (Williston Park) | Irinotecan activity across lymphoma, leukaemia, and breast, pancreatic, ovarian and lung cancers |
| 7786821 | 1995 | Phase 1 | Ann Oncol | Phase I and pharmacokinetic study of daily-for-three-days irinotecan in advanced solid tumours |
| 31398063 | 2019 | Review | Expert Rev Anticancer Ther | Sacituzumab govitecan for triple-negative breast cancer |
| 26101915 | 2015 | Preclinical | Oncotarget | Trop-2 as a target for the SN-38 antibody-drug conjugate |
Singapore Market Information
All 11 licences are single-ingredient products with valid status. Approved-indication text is not available in the licence records.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN15612P | IRINOX 100 (irinotecan HCl) 100 mg/5 mL | Infusion, solution concentrate | Not stated |
| SIN15397P | ONIVYDE pegylated liposomal irinotecan 4.3 mg/mL | Infusion, solution concentrate | Not stated |
| SIN09428P | CAMPTO for infusion 20 mg/mL | Injection | Not stated |
| SIN16797P | IRNIZET 100 100 mg/5 mL | Infusion, solution concentrate | Not stated |
| SIN15613P | IRINOX 40 (irinotecan HCl) 40 mg/2 mL | Infusion, solution concentrate | Not stated |
Six further irinotecan licences are registered (SIN15734P, SIN14373P, SIN15735P, SIN13367P, SIN16266P, SIN15701P); all are injectable or infusion concentrates.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (camptothecin class, topoisomerase I inhibitor) |
| Myelosuppression Risk | High. The knowledge graph lists neutropenia, thrombocytopenia, agranulocytosis and anaemia as contraindicated conditions. |
| Emetogenicity Classification | Moderate |
| Monitoring Items | CBC with differential, liver function (including bilirubin), renal function, electrolytes; monitor for diarrhoea |
| Handling Protection | Must follow cytotoxic drug handling regulations |
Please refer to the package insert warnings and precautions for formal classification.
Safety Considerations
- Conditions flagged as contraindications in the knowledge graph (not label text): kidney disease, liver disease, gallbladder disease, pancreatitis, pyoureter, thrombocytopenia, neutropenia, agranulocytosis, anaemia (including macrocytic), ileus, intestinal obstruction, hyperbilirubinaemia (including hereditary forms and Gilbert syndrome), interstitial lung disease, and diarrhoeal disease.
- Drug interactions: 100 interactions were found in total; the 20 reviewed include one Major interaction, with clarithromycin. Most of the others are Moderate, including aprepitant, dexamethasone, cimetidine, miconazole, metreleptin, eluxadoline, and a group of laxatives (bisacodyl, picosulfuric acid, magnesium salts, lactulose, lactitol, castor oil, glycerin, mannitol, mineral oil, phenolphthalein). Levofloxacin is Minor.
Please refer to the package insert for official warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The TxGNN score is high, and the SN-38 mechanism is validated in breast cancer through sacituzumab govitecan. However, direct evidence for irinotecan is limited to one small Phase 1 breast cancer study (n=12), a few mixed-tumour Phase 1 studies, and a recent Phase 2 liposomal irinotecan study. No completed Phase 3 trial supports it, so this remains a research question rather than a candidate for adoption.
To proceed, the following is needed:
- Results and full text of the PHENOMENAL Phase 2 study, plus any other direct irinotecan or liposomal irinotecan breast cancer trials
- Package insert warnings and contraindications from HSA (currently missing and blocking safety screening)
- Mechanism of action data from DrugBank
- A comparison against existing breast cancer standards, including sacituzumab govitecan, to establish a role for irinotecan itself
- Singapore-specific approved-indication text, and a decision on which formulation (conventional or liposomal) to study
- A safety monitoring plan covering neutropenia, diarrhoea, and liver function
Other predicted indications (all pancreatic subtypes of the approved pancreatic adenocarcinoma indication, with the highest-ranked first):
- Research Question (L3): rare pancreatic histologies including invasive IPMN carcinoma and IPMN (retrospective or case-level evidence from 2026), and pancreatic signet ring cell adenocarcinoma (one Phase 1 mFOLFIRINOX study).
- Hold (L4/L5): osteoclastic giant cell tumour, solid pseudopapillary carcinoma, mixed ductal-endocrine carcinoma, malignant exocrine pancreas neoplasm, and undifferentiated pancreatic carcinoma. These have no trials or only case reports, or a terminated study with one participant.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.