Irinotecan
| Evidence Level: L3 | Predicted Indications: 1 |
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 chemotherapy, originally used for metastatic colon cancer and pancreatic adenocarcinoma. The TxGNN model predicts it may be effective for female breast carcinoma, but the supporting evidence is mostly early-phase: 9 clinical trials (only 2 directly relevant, both Phase 1) and 20 publications, none showing Phase 3 results for irinotecan itself in breast cancer.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Metastatic colon cancer and pancreatic adenocarcinoma (from the knowledge graph; no approved indication text is available from New Zealand licences) |
| Predicted New Indication | Female breast carcinoma |
| TxGNN Prediction Score | 99.08% |
| Evidence Level | L3 |
| New Zealand Market Status | ✗ Cancelled only |
| Number of Authorizations | 5 (all cancelled) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the compiled data. Based on known pharmacology, irinotecan targets DNA topoisomerase I, and its active metabolite SN-38 causes DNA damage in rapidly dividing cells. This mechanism is not specific to one tumour type. The target mapping rests on structural similarity to camptothecin and topotecan rather than direct affinity data.
The strongest mechanistic support comes from sacituzumab govitecan, an anti-Trop-2 antibody-drug conjugate that delivers SN-38. It has been studied in metastatic breast cancer, including the Phase III TROPiCS-02 trial in HR+/HER2- disease. This supports the activity of the SN-38 payload in breast cancer but does not directly validate irinotecan itself.
Earlier literature describes irinotecan as having only marginal activity in breast cancer, with a rationale for sequential use with mitomycin, which upregulates topoisomerase I. The TxGNN score is a computational prediction, not clinical evidence.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00083148 | Phase 1 | Completed | 12 | Irinotecan followed by capecitabine in advanced breast carcinoma; directly relevant but small, giving limited safety and feasibility evidence |
| NCT00004095 | Phase 1 | Completed | 38 | Irinotecan plus gemcitabine in unresectable or metastatic solid tumours; not breast-specific |
| NCT00031681 | Phase 1 | Completed | 41 | UCN-01 plus irinotecan in resistant solid tumours, with a triple-negative breast cancer part |
| NCT05453825 | Phase 2 | Unknown | 180 | Navicixizumab alone or with paclitaxel or irinotecan in advanced solid tumours, including a triple-negative breast cancer cohort |
| NCT03678883 | Phase 2 | Active, not recruiting | 350 | 9-ING-41 (GSK-3β inhibitor) with chemotherapy in refractory cancers; irinotecan's role is unclear |
| NCT02419495 | Phase 1 | Terminated | 221 | Selinexor with several standard chemotherapies; focus is selinexor safety |
| NCT06840886 | Phase 1 | Recruiting | 426 | First-in-human study of PHST001 in advanced solid tumours; indirect relevance |
| NCT06769425 | Phase 1 | Recruiting | 157 | PARP1 inhibitor HS-10502 combinations in advanced solid tumours; indirect relevance |
| NCT05238831 | Early Phase 1 | Withdrawn | 0 | Precision-medicine adaptive pilot study; no participants, no usable evidence |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 41371050 | 2026 | Phase 2 study | Eur J Cancer | PHENOMENAL: liposomal irinotecan in HER2-negative breast cancer with brain metastases |
| 40877204 | 2025 | Clinical study | Cancer Rep | Etirinotecan pegol (PEGylated irinotecan-type agent) in active brain metastases from lung or breast cancer |
| 32223649 | 2020 | Trial design | Future Oncol | TROPiCS-02: Phase III design of sacituzumab govitecan (SN-38 conjugate) in HR+/HER2- metastatic breast cancer |
| 12800602 | 2003 | Review | Oncology (Williston Park) | Rationale for mitomycin and irinotecan in advanced breast cancer; marginal single-agent activity, preclinical synergy |
| 9726101 | 1998 | Review | Oncology (Williston Park) | Irinotecan activity across several tumours, including breast cancer |
| 25944802 | 2015 | Phase 1 | Clin Cancer Res | First-in-human trial of sacituzumab govitecan in diverse metastatic solid tumours |
| 28558150 | 2017 | Safety/PK report | Cancer | Safety and pharmacokinetics of sacituzumab govitecan in epithelial cancers |
| 40749148 | 2025 | Early-phase study | J Clin Oncol | DEP-SN38 nanoparticle conjugate in advanced solid tumours: safety and preliminary efficacy |
| 26101915 | 2015 | Preclinical | Oncotarget | Trop-2 as a target for the SN-38 conjugate sacituzumab govitecan |
| 19059062 | 2008 | Review | Clin Lab Med | Pharmacogenomics of irinotecan and tamoxifen (UGT1A1-related toxicity) |
New Zealand Market Information
All five authorizations are cancelled, and no approved indication text is available.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 2621177 | Accord | Inj 20 mg per ml, 5 ml vial | Not available |
| 2351013 | Irinotecan-Rex | Inj 20 mg per ml, 5 ml vial | Not available |
| 2711036 | Accord | Inj 20 mg per ml, 25 ml vial | Not available |
| 2401916 | Irinotecan Actavis 100 | Inj 20 mg per ml, 5 ml vial | Not available |
| 2204142 | Baxter | Inj 1 mg for ECP | Not available |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (topoisomerase I inhibitor) |
| Myelosuppression Risk | High (the knowledge graph lists neutropenia, thrombocytopenia, agranulocytosis and anaemia as contraindication-related conditions) |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | CBC with differential, liver function (including bilirubin), renal function; consider UGT1A1 genotyping given the pharmacogenomic literature |
| Handling Protection | Must follow cytotoxic drug handling regulations |
Safety Considerations
- Contraindication-related conditions (knowledge graph, not label text): kidney disease, pyoureter, pancreatitis, liver disease, gallbladder disease, thrombocytopenia, neutropenia, agranulocytosis, anaemia (including macrocytic anaemia), ileus, intestinal obstruction, hyperbilirubinaemia (including hereditary forms and Gilbert syndrome), interstitial lung disease and diarrhoeal disease.
- Drug Interactions: The interaction query returned one pharmacology entry, the target DNA topoisomerase I, and no interacting-drug data with severity levels.
Package insert warnings and contraindications could not be retrieved, so please refer to the package insert for the full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The evidence consists of small Phase 1 studies and indirect data from SN-38 antibody-drug conjugates, with no Phase 3 results for irinotecan in breast cancer. Irinotecan has also been described as having only marginal activity in this disease. All New Zealand licences are cancelled, and package insert safety data are missing. At this stage it is a research question rather than an actionable repurposing candidate.
To proceed, the following is needed:
- Medsafe package insert warnings and contraindications (blocking gap for safety screening)
- Mechanism of action data from DrugBank
- Results of the PHENOMENAL Phase 2 study and any randomised data on irinotecan or liposomal irinotecan in breast cancer
- Clarification of the regulatory and supply route, since no valid New Zealand licence currently exists
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.