Doxorubicin
| Evidence Level: L1 | Predicted Indications: 8 |
Table of Contents
- Doxorubicin
- Pharmacist Assessment Report
- Doxorubicin: topoisomerase II–inhibiting anthracycline → Ewing sarcoma
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- Canada Market Information
- Cytotoxicity
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Doxorubicin: topoisomerase II–inhibiting anthracycline → Ewing sarcoma
One-Sentence Summary
Doxorubicin is an anthracycline chemotherapy drug that damages DNA in rapidly dividing cancer cells. The TxGNN model predicts it may be useful for Ewing sarcoma, with 29 clinical trials and 20 publications compiled for this report, including several Phase 3 trials of multi-drug regimens that contain doxorubicin.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Ewing sarcoma |
| TxGNN Prediction Score | 0.9990 |
| Evidence Level | L1 |
| Canada Market Status | Marketed (marketed DINs: 7 of 7) |
| Number of DINs | 7 (marketed: 7) |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data was not available in the data compiled for this report. From general pharmacology, doxorubicin is a topoisomerase II poison and DNA intercalator, and it is active against rapidly proliferating small round cell sarcomas.
Doxorubicin is a backbone of standard multi-agent Ewing sarcoma regimens, such as vincristine–doxorubicin–cyclophosphamide (VDC) alternating with ifosfamide–etoposide (IE). Several Phase 3 trials of these regimens, including interval-compressed chemotherapy, EURO-EWING 99 and a ganitumab combination trial, include doxorubicin. This is therefore partly an extension of established use rather than a wholly new idea. A limit of the evidence is that doxorubicin is given inside combinations, so its individual contribution is hard to separate.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00006734 | Phase 3 | Completed | 587 | Interval-compressed chemotherapy in Ewing sarcoma and related tumours |
| NCT01231906 | Phase 3 | Completed | 642 | Adding vincristine–topotecan–cyclophosphamide to a standard 5-drug regimen (including doxorubicin) in non-metastatic disease |
| NCT02063022 | Phase 3 | Completed | 278 | Dose intensification vs standard treatment in non-metastatic Ewing sarcoma |
| NCT02306161 | Phase 3 | Active, not recruiting | 312 | Ganitumab added to multi-agent chemotherapy in metastatic Ewing sarcoma |
| NCT00020566 | Phase 3 | Unknown | 1200 | EURO-E.W.I.N.G.99: chemotherapy with or without radiotherapy, surgery or stem cell transplant |
| NCT00002466 | Phase 2 | Completed | Not reported | Combination chemotherapy including doxorubicin, followed by resection and radiotherapy, in peripheral primitive neuroectodermal tumours and Ewing sarcoma |
| NCT00003667 | Phase 2 | Completed | Not reported | Randomized vincristine–doxorubicin–cyclophosphamide–dexrazoxane with or without ImmTher in high-risk disease |
| NCT00038142 | Phase 2 | Terminated | 46 | Same regimen as above; terminated early |
| NCT01864109 | Phase 2 | Active, not recruiting | 83 | Irinotecan and temozolomide added to alkylator-based chemotherapy |
| NCT06820957 | Phase 2/3 | Terminated | 2 | VIrR added to VDC/IE in metastatic Ewing sarcoma; terminated with very few patients |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 12594313 | 2003 | RCT | N Engl J Med | Adding ifosfamide and etoposide to standard chemotherapy for newly diagnosed Ewing sarcoma |
| 36522207 | 2022 | RCT | Lancet | EE2012: comparison of two chemotherapy regimens in newly diagnosed Ewing sarcoma |
| 36669140 | 2023 | RCT | J Clin Oncol | Ganitumab with interval-compressed chemotherapy in metastatic Ewing sarcoma |
| 23091096 | 2012 | RCT | J Clin Oncol | Interval-compressed chemotherapy in localized Ewing sarcoma |
| 31952545 | 2020 | RCT protocol | Trials | EURO EWING 2012 protocol |
| 37403815 | 2023 | Review | Cancer | Consensus recommendations for Ewing sarcoma management |
| 26304893 | 2015 | Review | J Clin Oncol | Current management and future approaches |
| 20152770 | 2010 | Review | Lancet Oncol | Survival rose from about 10% to about 75% for localized disease with chemotherapy |
| 1833556 | 1991 | Dose-intensity analysis | J Natl Cancer Inst | Influence of doxorubicin dose intensity on response and outcome in osteogenic and Ewing sarcoma |
| 37651654 | 2023 | Long-term follow-up | J Clin Oncol | Long-term outcomes with interval-compressed chemotherapy (AEWS0031) |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02194465 | Doxorubicin Hydrochloride for Injection USP | Not recorded | Not recorded |
| 02194473 | Doxorubicin Hydrochloride for Injection USP | Not recorded | Not recorded |
| 02410397 | Doxorubicin | Not recorded | Not recorded |
| 02238389 | Caelyx | Not recorded | Not recorded |
| 02493020 | Taro-Doxorubicin Liposomal | Not recorded | Not recorded |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (anthracycline) |
| Myelosuppression Risk | High; neutropenia, leukopenia, thrombocytopenia and anaemia are relevant concerns |
| Emetogenicity Classification | Moderate to high |
| Monitoring Items | CBC with differential, liver function (including bilirubin), renal function, cardiac function (echocardiography; cumulative dose tracking) |
| Handling Protection | Must follow cytotoxic drug handling regulations |
Safety Considerations
- Contraindication-related conditions (from drug–disease relationship data, not label text): liver failure and liver disease, thrombocytopenia, neutropenia, leukopenia, agranulocytosis, anaemia, heart disease, cardiomyopathy, congestive heart failure, heart failure, sudden cardiac arrest, heart conduction disease, hyperbilirubinaemia, and infectious diseases. These point mainly to cardiac, hepatic and bone marrow risks and should be checked against the product label.
- Drug Interactions: 100 interactions were found. Major-level examples include dolasetron, cisapride and papaverine. Moderate examples include ondansetron, granisetron, palonosetron, aprepitant, dexamethasone, clarithromycin, levofloxacin and famotidine. Some of these (e.g. 5-HT3 antagonists) are commonly co-prescribed as supportive care, so QT and other effects need review.
- Cardiotoxicity: The literature highlights anthracycline-related cardiotoxicity. Cumulative dose limits, dexrazoxane and echocardiographic monitoring are suggested guardrails.
Please also refer to the package insert, because label warnings were not available in the data compiled for this report.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Several completed Phase 3 randomized trials and RCT publications study Ewing sarcoma regimens that contain doxorubicin, and it is part of standard multi-agent therapy. The evidence is for combinations, not doxorubicin alone, and its cardiac and bone marrow toxicity needs active management.
To proceed, the following is needed:
- Package insert warnings and contraindications from Health Canada
- Mechanism-of-action data from DrugBank
- A cardiac monitoring plan (cumulative dose limits, dexrazoxane use, echocardiography)
- Confirmation of the Canadian labelled indications for each product, as they are not recorded in the local data
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.