Irinotecan
| Evidence Level: L5 | Predicted Indications: 1 |
Table of Contents
- Irinotecan
- Pharmacist Assessment Report
- Irinotecan: From Metastatic Colon Cancer and Pancreatic Adenocarcinoma to Female Breast Carcinoma
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- India Market Information
- Cytotoxicity
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
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 colorectal cancer and pancreatic adenocarcinoma. The TxGNN model predicts it may be effective for female breast carcinoma, but the supporting evidence is limited: of 9 clinical trials listed, only one directly tests irinotecan in breast cancer (a 12-patient Phase 1 study), and most of the 20 publications concern related compounds such as SN-38 conjugates.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Metastatic colon cancer; pancreatic adenocarcinoma |
| Predicted New Indication | Female breast carcinoma |
| TxGNN Prediction Score | 0.9908 |
| Evidence Level | L5 |
| India Market Status | Listed in a compiled Indian medicine price dataset (at least 20) – CDSCO approval status is not included in this data |
| Number of Listed Products | at least 20 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, 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 single-strand breaks that become lethal double-strand breaks during DNA replication. Its efficacy in colorectal and pancreatic cancers is established.
Breast carcinoma cells, particularly rapidly proliferating subtypes such as triple-negative disease, may be sensitive to this mechanism. Indirect support comes from sacituzumab govitecan, an anti-Trop-2 antibody-drug conjugate carrying SN-38, which has shown clinical benefit in metastatic breast cancer. This shows that SN-38 activity is relevant to the disease, but it is not direct evidence for irinotecan as a free drug.
The high TxGNN score is a computational prediction only. Irinotecan-specific clinical data in breast cancer are limited to small Phase 1 studies in combination settings. A literature review from 2003 also describes irinotecan as having only marginal single-agent activity in breast cancer, with preclinical synergy when sequenced after mitomycin.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00083148 | Phase 1 | Completed | 12 | Irinotecan followed by capecitabine in advanced breast carcinoma. The only trial directly testing irinotecan in the target disease; dose-finding and safety only |
| NCT00031681 | Phase 1 | Completed | 41 | UCN-01 plus irinotecan in resistant solid tumours, with a triple-negative breast cancer part; informs combination safety |
| NCT00004095 | Phase 1 | Completed | 38 | Irinotecan plus gemcitabine in mixed solid tumours; no breast-specific efficacy readout |
| NCT03678883 | Phase 2 | Active, not recruiting | 350 | GSK-3β inhibitor 9-ING-41 alone or with chemotherapy (irinotecan is one possible partner) in refractory cancers |
| NCT05453825 | Phase 2 | Unknown | 180 | Navicixizumab basket study with paclitaxel or irinotecan, including a triple-negative breast cancer cohort; irinotecan relevance is indirect |
| NCT02419495 | Phase 1 | Terminated | 221 | Selinexor with standard chemotherapies, possibly including irinotecan; breast-specific data unclear |
| NCT06840886 | Phase 1 | Recruiting | 426 | First-in-human study of PHST001 in solid tumours; irinotecan not the focus |
| NCT06769425 | Phase 1 | Recruiting | 157 | PARP1 inhibitor HS-10502 combination treatment; irinotecan link is indirect |
| NCT05238831 | Early Phase 1 | Withdrawn | 0 | Precision-medicine adaptive trial; withdrawn with no participants, so 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; the formulation crosses the blood-brain barrier |
| 32223649 | 2020 | RCT protocol (Phase 3) | 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 |
| 40877204 | 2025 | Clinical study | Cancer Rep | Etirinotecan pegol (a PEGylated irinotecan-type agent) in active brain metastases from lung or breast cancer |
| 40749148 | 2025 | Early-phase trial | J Clin Oncol | Dendrimer-nanoparticle SN-38 (DEP-SN38) in advanced solid tumours: safety and preliminary efficacy |
| 12800602 | 2003 | Review | Oncology (Williston Park) | Rationale for mitomycin plus irinotecan in advanced breast cancer; marginal single-agent activity, preclinical synergy |
| 9726101 | 1998 | Review | Oncology (Williston Park) | Irinotecan activity across lymphoma, leukaemia, breast, pancreatic, ovarian and small-cell lung cancers |
| 19059062 | 2008 | Review | Clin Lab Med | Pharmacogenomics of tamoxifen and irinotecan, including UGT1A1-linked toxicity |
| 28558150 | 2017 | Safety/PK analysis | Cancer | Safety and pharmacokinetics of sacituzumab govitecan across epithelial cancers |
| 40818326 | 2026 | Preclinical | Biomaterials | Copper-irinotecan nanodrug-bacteria biohybrid for breast cancer immunotherapy |
India Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 58230 | Campto 100mg Injection (Pfizer Ltd) | Injection, vial of 5 ml | Not specified |
| 131450 | Lilrincan 100mg Injection (Eli Lilly and Company India Pvt Ltd) | Injection, vial | Not specified |
| 108457 | Irnocam 100mg Injection (Dr Reddy’s Laboratories Ltd) | Injection, vial | Not specified |
| 113551 | Irnozen 20mg Injection (Sun Pharmaceutical Industries Ltd) | Injection, vial | Not specified |
| 112727 | Imtus 40mg Injection (Emcure Pharmaceuticals Ltd) | Injection, vial of 1 ml | Not specified |
Twenty valid single-ingredient registrations exist in total; the five above are shown as examples.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (topoisomerase I inhibitor, camptothecin class) |
| Myelosuppression Risk | High (neutropenia, thrombocytopenia and anaemia are listed among contraindication-linked conditions in the knowledge graph) |
| Emetogenicity Classification | Moderate |
| Monitoring Items | CBC with differential, liver function (including bilirubin), renal function, electrolytes, diarrhoea and hydration status |
| Handling Protection | Must follow cytotoxic drug handling regulations |
Safety Considerations
- Contraindication-linked conditions (from the knowledge graph, not label text): kidney disease, liver disease, hyperbilirubinaemia (including hereditary forms and Gilbert syndrome), pancreatitis, gallbladder disease, thrombocytopenia, neutropenia, agranulocytosis, anaemia, ileus and intestinal obstruction, interstitial lung disease, diarrhoeal disease, and pyoureter.
- Drug Interactions: 435 interactions were identified. Notable examples:
- Major: clarithromycin.
- Moderate: aprepitant, dexamethasone, cimetidine, miconazole, eluxadoline, metreleptin, and numerous laxatives and osmotic agents (bisacodyl, picosulfuric acid, magnesium salts, lactulose, lactitol, castor oil, glycerin, mannitol, mineral oil, phenolphthalein).
- Minor: levofloxacin.
Please also refer to the package insert for label warnings and contraindications, which were not available for this report.
Conclusion and Next Steps
Decision: Hold
Rationale: The TxGNN score is high (0.9908), but the evidence is indirect. Only one small Phase 1 trial (n=12) tests irinotecan in breast cancer, no efficacy trial exists, and most of the literature concerns SN-38 conjugates or liposomal formulations rather than conventional irinotecan. The mechanism is plausible, so this remains a research question rather than a candidate for advancement.
To proceed, the following is needed:
- Package insert warnings and contraindications from the India registrations, which are required before any safety screening
- Detailed mechanism of action data from DrugBank
- Results from the PHENOMENAL Phase 2 study and from the completed breast cancer Phase 1 trials (NCT00083148, NCT00031681)
- Evaluation of whether free irinotecan, rather than SN-38 conjugates or liposomal forms, offers benefit in specific breast cancer subtypes such as triple-negative disease
- Confirmation of route and formulation compatibility (all registered products in India are injectables)
- A UGT1A1 genotyping and diarrhoea/neutropenia management plan
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.