Irinotecan

Evidence Level: L5

Predicted Indications: 1

Irinotecan

Pharmacist Assessment Report

Irinotecan: 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 supporting evidence is mostly early-phase or indirect: 9 clinical trials (only one directly tests irinotecan in breast cancer, a Phase 1 study with 12 patients) and 20 publications were compiled.

Quick Overview

Item	Content
Original Indication	Not recorded in the local data
Predicted New Indication	Female breast carcinoma
TxGNN Prediction Score	0.9908
Evidence Level	L5
Australia Market Status	Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data
Number of PBS Items	1 (valid: 1)
Recommended Decision	Hold

Why is This Prediction Reasonable?

Detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, irinotecan is a topoisomerase I inhibitor. Its active metabolite, SN-38, causes DNA damage in rapidly dividing tumour cells.

Breast carcinoma has an indirect link to this mechanism. Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate that carries SN-38, is clinically validated in breast cancer, including HR+/HER2- metastatic disease. This shows topoisomerase I inhibition is a pharmacologically valid approach in breast cancer. It is not direct evidence for irinotecan itself.

Direct evidence for irinotecan is limited. One older review described irinotecan and mitomycin as having only marginal activity in advanced breast cancer, although preclinical work suggested synergy. A recent Phase 2 study (PHENOMENAL, 2026) of liposomal irinotecan in HER2-negative breast cancer with brain metastases is the most relevant newer signal. Its abstract in the compiled data did not include results, and liposomal irinotecan is a different formulation from the product registered in Australia.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrolment	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 part
NCT00004095	Phase 1	Completed	38	Irinotecan plus gemcitabine in unresectable or metastatic solid tumours. Not breast-specific
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 1/2	Active, not recruiting	350	GSK-3β inhibitor 9-ING-41 alone or with chemotherapy. Irinotecan is a possible partner
NCT02419495	Phase 1	Terminated	221	Selinexor with several standard chemotherapies, irinotecan among them
NCT06840886	Phase 1	Recruiting	426	PHST001 in advanced solid tumours. Irinotecan involvement is unclear
NCT06769425	Phase 1	Recruiting	157	PARP1 inhibitor HS-10502 combinations. Irinotecan relevance is indirect
NCT05238831	Early Phase 1	Withdrawn	0	Precision-medicine adaptive study. No participants enrolled, so no usable evidence

No ANZCTR trials were identified in the data compiled for this report.

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. Liposomal irinotecan is reported to cross the blood-brain barrier
32223649	2020	Phase III protocol	Future Oncol	TROPiCS-02: sacituzumab govitecan (SN-38 conjugate) in HR+/HER2- metastatic breast cancer
25944802	2015	Phase 1/2	Clin Cancer Res	First-in-human trial of sacituzumab govitecan in diverse metastatic solid tumours
12800602	2003	Review	Oncology (Williston Park)	Rationale for mitomycin and irinotecan in advanced breast cancer. Both have marginal single-agent activity, with preclinical synergy
9726101	1998	Review	Oncology (Williston Park)	Irinotecan activity across lymphoma, leukaemia and breast, pancreatic, ovarian and lung cancers
28558150	2017	Safety/PK report	Cancer	Safety and pharmacokinetics of sacituzumab govitecan in advanced epithelial cancers
26101915	2015	Preclinical	Oncotarget	Trop-2 as a target for the SN-38 antibody-drug conjugate
19059062	2008	Review	Clin Lab Med	Pharmacogenomics of tamoxifen and irinotecan, including UGT1A1-linked irinotecan toxicity
40749148	2025	Early-phase trial	J Clin Oncol	Dendrimer-nanoparticle SN38 in advanced solid tumours
40818326	2026	Preclinical	Biomaterials	Copper-irinotecan nanodrug-bacteria hybrid in breast cancer models

Much of this literature concerns SN-38 conjugates or novel formulations, not irinotecan itself.

Australia Market Information

ARTG Number	Product Name	Dosage Form	Approved Indication
ARTG 4451G	Irinotecan Accord	I.V. injection containing irinotecan hydrochloride trihydrate 500 mg in 25 mL	Indication text not available in the data compiled for this report

Cytotoxicity

Item	Content
Cytotoxicity Classification	Conventional cytotoxic (topoisomerase I inhibitor)
Myelosuppression Risk	Please refer to the Product Information (PI). The knowledge graph links irinotecan to neutropenia, thrombocytopenia and anaemia as contraindication-related conditions
Emetogenicity Classification	Please refer to the Product Information (PI) warnings and precautions
Monitoring Items	Full blood count with differential, liver function (including bilirubin) and renal function, per the PI
Handling Protection	Must follow local cytotoxic drug handling requirements

Safety Considerations

Knowledge-graph contraindication signals (these come from the TxGNN knowledge graph, not from TGA label text, and must be confirmed against the PI): kidney disease, liver disease, gallbladder disease, pancreatitis, hyperbilirubinaemia (including Gilbert syndrome), thrombocytopenia, neutropenia, agranulocytosis, anaemia, ileus, intestinal obstruction, interstitial lung disease and diarrhoeal disease.
Drug interactions (100 recorded; main ones listed):
- Major: clarithromycin.
- Moderate: aprepitant, dexamethasone, cimetidine, miconazole, eluxadoline, metreleptin, and many laxatives and osmotic agents (bisacodyl, picosulfuric acid, magnesium salts, lactulose, lactitol, castor oil, glycerin, mannitol, mineral oil, phenolphthalein).
- Minor: levofloxacin.

Label warnings and contraindications were not available. Please refer to the TGA-approved Product Information (PI) for full safety information.

Conclusion and Next Steps

Decision: Hold

Rationale: The mechanism is plausible and the TxGNN score is high, but direct evidence for irinotecan in breast cancer is limited to one small Phase 1 trial and older reviews. Most supporting data concern SN-38 antibody-drug conjugates or liposomal and experimental formulations, which cannot be extrapolated to the registered product. Label safety data are also missing.

To proceed, the following is needed:

Phase 2 or larger efficacy data for irinotecan itself in breast cancer, including results from the liposomal irinotecan PHENOMENAL study
A clear comparison of the benefit of conventional irinotecan against established breast cancer options, including sacituzumab govitecan
The TGA Product Information to confirm indications, warnings and contraindications
Detailed mechanism of action data
A plan for UGT1A1 genotype-guided dosing and monitoring for neutropenia and diarrhoea

Other Predicted Indications (Brief Note)

Several other predictions are pancreatic cancer subtypes, which overlap with the original pancreatic indication and are mostly supported by retrospective or case-level reports. They are therefore not distinct repurposing opportunities. Lower-ranked predictions with no supporting trials or literature (osteoclastic giant cell tumour of the pancreas, mixed ductal-endocrine carcinoma) should stay on Hold.

Disclaimer

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