Doxorubicin
| 證據等級: L5 | 預測適應症: 10 個 |
目錄
Doxorubicin: From Broad-Spectrum Antineoplastic Use to Ewing Sarcoma
One-Sentence Summary
Doxorubicin is a well-established anthracycline chemotherapy agent used across a broad range of malignancies. The TxGNN model predicts it may be effective for Ewing sarcoma, with 48 clinical trials and 20 publications currently supporting this direction — a substantially larger evidence base than any of the other candidate indications generated for this drug.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not documented in this evidence pack (no original indication or license records available) |
| Predicted New Indication | Ewing sarcoma |
| TxGNN Prediction Score | 99.90% |
| Evidence Level | L1 |
| US Market Status | ✗ Not Marketed |
| Number of NDAs | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action (MOA) data is not available for doxorubicin in this evidence pack. Based on known information, doxorubicin belongs to the anthracycline class of conventional cytotoxic chemotherapy agents, which intercalate DNA and inhibit topoisomerase II to block tumor cell replication. This class of drug has broad, well-documented antineoplastic activity across many solid tumor and hematologic malignancy types.
The volume of clinical trial and literature evidence returned for Ewing sarcoma is unusually large for a “predicted” indication — 48 registered trials and 20 publications, including multiple completed Phase 3 randomized controlled trials. This strongly suggests that doxorubicin is not a novel repurposing candidate for this disease but rather an already deeply embedded component of standard-of-care multi-agent regimens (commonly referred to as VDC — vincristine, doxorubicin, cyclophosphamide — alternating with ifosfamide/etoposide). The TxGNN model’s high-confidence score is therefore well corroborated by real-world evidence.
Mechanistically, Ewing sarcoma is a highly chemosensitive small round cell malignancy, and cytotoxic DNA-damaging agents such as doxorubicin have long formed the backbone of curative-intent multimodal therapy (chemotherapy plus surgery and/or radiotherapy) in this disease, consistent with the pattern seen in the supporting trials and literature below.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01231906 | Phase 3 | Completed | 642 | RCT testing addition of vincristine-topotecan-cyclophosphamide to standard 5-drug regimen (incl. doxorubicin) in non-metastatic Ewing sarcoma |
| NCT00006734 | Phase 3 | Completed | 587 | Compared chemotherapy intensification regimens combined with radiotherapy and/or surgery in Ewing’s sarcoma/PNET |
| NCT02063022 | Phase 3 | Completed | 278 | RCT comparing standard vs. dose-intensified induction/maintenance chemotherapy in non-metastatic Ewing sarcoma |
| NCT02306161 | Phase 3 | Active, not recruiting | 312 | RCT evaluating addition of IGF-1R antibody ganitumab to standard VDC/IE chemotherapy in newly diagnosed metastatic Ewing sarcoma |
| NCT06820957 | Phase 2/3 | Active, not recruiting | 437 | RCT comparing VIrR added to standard VDC/IE regimen vs. VDC/IE alone in newly diagnosed metastatic Ewing sarcoma |
| NCT00020566 | Phase 3 | Unknown | 1200 | EURO-E.W.I.N.G.99: RCT of combination chemotherapy with/without radiotherapy and high-dose stem cell-supported consolidation |
| NCT00002516 | Phase 3 | Unknown | N/A | EICESS-92: RCT comparing combination chemotherapy regimens plus surgery/radiotherapy for Ewing’s sarcoma |
| NCT02727387 | Phase 2 | Completed | 155 | High-dose chemotherapy, radiotherapy and cyclophosphamide/anti-COX2 consolidation for metastatic Ewing sarcoma |
| NCT03011528 | Phase 2 | Completed | 45 | First-line multidisciplinary chemotherapy strategy for Ewing tumours with primary extrapulmonary dissemination |
| NCT06699472 | Phase 2 | Recruiting | 22 | RCT of prophylactic Trilaciclib to prevent VDC/IE chemotherapy-related myelosuppression in Ewing’s sarcoma |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 36522207 | 2022 | RCT | Lancet | EE2012 trial comparing two international standard chemotherapy strategies for newly diagnosed Ewing sarcoma |
| 36669140 | 2023 | RCT | J Clin Oncol | COG AEWS1221: addition of ganitumab to interval-compressed chemotherapy did not improve event-free survival in metastatic Ewing sarcoma |
| 23091096 | 2012 | RCT | J Clin Oncol | COG trial showing interval-compressed VDC/IE chemotherapy improves outcome in localized Ewing sarcoma |
| 12594313 | 2003 | RCT | N Engl J Med | Landmark trial: addition of ifosfamide/etoposide to standard doxorubicin-based regimen improves survival in Ewing’s sarcoma/PNET |
| 31952545 | 2020 | Trial Protocol | Trials | Protocol for EURO EWING 2012 international RCT comparing induction/consolidation chemotherapy regimens |
| 37651654 | 2023 | Trial Update | J Clin Oncol | Long-term outcomes of interval-compressed chemotherapy from COG study AEWS0031 |
| 20152770 | 2010 | Review | Lancet Oncol | Overview of Ewing’s sarcoma treatment progress; multidisciplinary chemotherapy raised localized-disease survival from ~10% to ~75% |
| 37403815 | 2023 | Review | Cancer | Consensus recommendations from the National Ewing Sarcoma Tumor Board on standard-of-care management |
| 26304893 | 2015 | Review | J Clin Oncol | Review of current management and future collaborative directions in Ewing sarcoma |
| 25993235 | 2015 | Review | ASCO Educ Book | Overview of systemic chemotherapy backbones (including doxorubicin-based VDC/IE) for osteosarcoma and Ewing sarcoma |
US Market Information
No market authorization records are currently on file for this drug in the evidence pack (0 licenses, market status: Not Marketed). This should be independently verified against the relevant regulatory database before further action.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic chemotherapy (anthracycline class; topoisomerase II inhibitor / DNA intercalator) |
| Myelosuppression Risk | High — supported by dedicated supportive-care trials in this evidence base, including NCT06699472 (Trilaciclib to prevent VDC/IE-related myelosuppression) and NCT07048249 (romiplostim to prevent chemotherapy-induced thrombocytopenia) in Ewing sarcoma patients |
| Emetogenicity Classification | High (typical of anthracycline-containing multi-agent regimens) |
| Monitoring Items | CBC with differential, cardiac function (baseline and serial LVEF/echocardiography, cardiac troponin per NCT01112800), liver and renal function, cumulative lifetime dose tracking |
| Handling Protection | Must follow cytotoxic/hazardous drug handling regulations; vesicant precautions against extravasation during administration |
Safety Considerations
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: Although the clinical evidence for doxorubicin in Ewing sarcoma is exceptionally strong (Evidence Level L1, with multiple completed Phase 3 RCTs and consistent literature support reflecting its role as a backbone agent in standard multi-agent chemotherapy), the evaluation cannot proceed to a full safety review. The TFDA-equivalent warnings/contraindications data is a Blocking-severity gap that directly prevents entry into the S1 safety initial evaluation, and no current market authorization (0 licenses) is on record for this drug in this jurisdiction.
To proceed, the following is needed:
- TFDA (or equivalent) package insert data — warnings and contraindications (Blocking gap, source: official regulatory site, method: download and parse label PDF)
- Detailed mechanism of action (MOA) data via DrugBank API query
- Confirmation of current market/license status in the target jurisdiction
- Completion of the drug-drug interaction (DDI) database query (currently not found)
- A cardiac monitoring protocol given the known cardiotoxicity risk associated with cumulative anthracycline dosing
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.