Irinotecan
| 證據等級: L5 | 預測適應症: 1 個 |
目錄
Irinotecan: From Colorectal Cancer (Established Use) to Female Breast Carcinoma
Note: This evidence pack contains no Taiwan/US regulatory license records and no
original_indicationsentries for irinotecan. “Colorectal cancer” above reflects irinotecan’s widely documented pharmacological use (general knowledge), not data extracted from this evidence pack.
One-Sentence Summary
Irinotecan is a topoisomerase I inhibitor best known as a component of colorectal cancer chemotherapy regimens (e.g., FOLFIRI). The TxGNN model predicts it may be effective for Female Breast Carcinoma, supported by 22 clinical trials and 20 publications, though the drug currently has no marketing authorization on file in this evidence pack.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available in evidence pack (taiwan_regulatory.licenses and original_indications are both empty) |
| Predicted New Indication | Female Breast Carcinoma |
| TxGNN Prediction Score | 99.08% |
| Evidence Level | L2 (1 completed Phase 2 randomized trial of irinotecan monotherapy in breast cancer) |
| US Market Status | Not Marketed |
| Number of NDAs | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available for irinotecan in this evidence pack (original_moa: [Data Gap]). Based on generally established pharmacology, irinotecan is a semi-synthetic camptothecin analog that is metabolized to SN-38, its active metabolite, which inhibits topoisomerase I and causes lethal DNA double-strand breaks during replication — its efficacy in colorectal cancer and other solid tumors is well documented.
Female breast carcinoma is mechanistically plausible as a repurposing target because SN-38 (irinotecan’s active metabolite) is the payload of sacituzumab govitecan, an antibody-drug conjugate now approved for triple-negative and HR+/HER2- metastatic breast cancer. This validates that SN-38-mediated topoisomerase I inhibition is an active mechanism in breast cancer biology, even though the ADC delivers the payload via a Trop-2-targeting antibody rather than as free irinotecan.
Directly, irinotecan itself has been tested as monotherapy and in combination (with capecitabine, gemcitabine, or targeted agents) in metastatic and triple-negative breast cancer in multiple Phase 1/2 trials, providing direct — not just mechanistic — supporting evidence for this indication.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00072852 | Phase 2 | Completed | 134 | Randomized trial of two irinotecan dosing schedules in metastatic breast cancer after anthracycline/taxane/capecitabine failure |
| NCT03562390 | Phase 2 | Unknown | 124 | Single-arm trial of third-line-or-later irinotecan in locally recurrent/metastatic breast cancer (Chinese patients) |
| NCT00083148 | Phase 1 | Completed | 12 | Irinotecan followed by capecitabine in advanced breast carcinoma; dose-finding |
| NCT00031681 | Phase 1 | Completed | 41 | Irinotecan + UCN-01 (7-hydroxystaurosporine) in triple-negative recurrent breast cancer |
| NCT05453825 | Phase 2 | Unknown | 180 | Navicixizumab monotherapy or with paclitaxel/irinotecan, including a TNBC cohort |
| NCT01631552 | Phase 1/2 | Completed | 515 | IMMU-132 (SN-38 antibody-drug conjugate) safety/efficacy in epithelial cancers |
| NCT04640480 | Phase 1 | Completed | 21 | SNB-101, a nano-particle formulation of SN-38, in advanced solid tumors |
| NCT01770353 | Phase 1 | Completed | 45 | Nanoliposomal irinotecan (MM-398/nal-IRI); tumor drug level and imaging feasibility study |
| NCT00004095 | Phase 1 | Completed | 38 | Irinotecan (CPT-11) + gemcitabine in solid tumors |
| NCT02033551 | Phase 1 | Completed | 47 | Veliparib alone or with carboplatin/paclitaxel or FOLFIRI (irinotecan-containing) in solid tumors |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 30786188 | 2019 | RCT | N Engl J Med | ASCENT trial: sacituzumab govitecan-hziy (SN-38 conjugate) improves outcomes in refractory metastatic triple-negative breast cancer |
| 36027558 | 2022 | RCT | J Clin Oncol | Sacituzumab govitecan in HR+/HER2- metastatic breast cancer |
| 28291390 | 2017 | Clinical trial | J Clin Oncol | Sacituzumab govitecan efficacy/safety in heavily pretreated metastatic TNBC |
| 32727805 | 2020 | Pilot study | Anticancer Res | Irinotecan + S-1 (IRIS) pilot study for advanced/metastatic breast cancer |
| 9726101 | 1998 | Review | Oncology (Williston Park) | Irinotecan activity across tumor types, including breast cancer |
| 12800602 | 2003 | Review | Oncology (Williston Park) | Rationale for mitomycin + irinotecan combination in advanced breast cancer |
| 36302269 | 2022 | Review | Breast (Edinburgh) | Clinical development of TROP-2-targeting antibody-drug conjugates in metastatic breast cancer |
| 35882754 | 2022 | Preclinical | Breast Cancer (Tokyo) | Trop-2 expression alteration in breast cancer cells by therapeutic agents and tamoxifen resistance |
| 39768216 | 2024 | Review | Cells | Sacituzumab govitecan in refractory triple-negative breast cancer precision medicine |
| 25944802 | 2015 | Clinical trial | Clin Cancer Res | First-in-human trial of anti-Trop-2/SN-38 conjugate sacituzumab govitecan in diverse metastatic solid tumors |
US Market Information
Currently no marketing authorization records are available — taiwan_regulatory.market_status is “未上市” (Not Marketed) with 0 total licenses on file in this evidence pack.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (Topoisomerase I inhibitor, camptothecin class) — based on general pharmacological classification, since DrugBank MOA/category data is not available in this evidence pack |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Please refer to the package insert warnings and precautions |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: A completed randomized Phase 2 trial and a supportive literature base (including two completed Phase 3 RCTs for the mechanistically related SN-38 antibody-drug conjugate class) suggest a plausible signal for irinotecan in breast cancer. However, the drug has no Taiwan/US marketing authorization on file, and the missing TFDA label/warnings data is flagged as a Blocking gap that prevents any S1 safety assessment.
To proceed, the following is needed:
- TFDA (or equivalent) product label with warnings, precautions, and contraindications (Blocking gap DG001)
- Confirmed DrugBank mechanism of action data (High-priority gap DG002)
- Drug-drug interaction (DDI) data — current query returned no results
- Route compatibility assessment between original and predicted-indication use
- Formal relevance grading of the listed clinical trials and literature (currently marked “pending”)
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.