Doxorubicin
| Evidence Level: L1 | Predicted Indications: 8 |
Table of Contents
- Doxorubicin
- Pharmacist Assessment Report
- Doxorubicin: Topoisomerase II inhibitor and DNA-intercalating anthracycline → Ewing sarcoma
- 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
Doxorubicin: Topoisomerase II inhibitor and DNA-intercalating anthracycline → Ewing sarcoma
One-Sentence Summary
Doxorubicin is an anthracycline chemotherapy drug that damages the DNA of rapidly dividing cancer cells. The TxGNN model predicts it may be effective for Ewing sarcoma, and the data compiled for this report include 28 clinical trials (several Phase 3) and 20 publications (including several randomized trials) in this disease.
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 |
| 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 | Proceed with Guardrails |
Why is This Prediction Reasonable?
Doxorubicin is a topoisomerase II inhibitor and DNA intercalator. It blocks the enzyme cancer cells need to copy and repair their DNA, so fast-dividing cells stop growing or die. The data compiled for this report do not include a separate formal mechanism-of-action record, but this mechanism is well described in the literature summarised below.
Ewing sarcoma is a fast-growing small round cell tumour of bone and soft tissue, mainly affecting children, adolescents and young adults. Doxorubicin is already a backbone of standard multi-agent regimens for this disease (vincristine–doxorubicin–cyclophosphamide alternating with ifosfamide–etoposide). The cytotoxic mechanism fits this tumour type well. Cumulative anthracycline heart toxicity is the main limit on use and requires cardiac monitoring and dose caps.
Clinical Trial Evidence
Doxorubicin-containing regimens have been tested in many Ewing sarcoma trials. The most relevant are listed below.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00006734 | Phase 3 | Completed | 587 | Randomized comparison of chemotherapy intensification through interval compression in Ewing sarcoma and related tumours |
| NCT01231906 | Phase 3 | Completed | 642 | Adding vincristine–topotecan–cyclophosphamide to standard 5-drug chemotherapy (including doxorubicin) in non-metastatic Ewing sarcoma |
| NCT02063022 | Phase 3 | Completed | 278 | Standard versus intensive treatment in non-metastatic Ewing sarcoma |
| NCT02306161 | Phase 3 | Active, not recruiting | 312 | Ganitumab added to multi-agent chemotherapy (including doxorubicin) in newly diagnosed metastatic Ewing sarcoma |
| NCT00020566 | Phase 3 | Unknown | 1200 | EURO-E.W.I.N.G.99: chemotherapy with or without radiotherapy, surgery or stem cell transplantation |
| NCT00002516 | Phase 3 | Unknown | Not reported | EICESS 92: comparison of combination chemotherapy regimens plus surgery and radiotherapy |
| NCT00002466 | Phase 2 | Completed | Not reported | Cyclophosphamide, doxorubicin, vincristine, etoposide and ifosfamide followed by resection and radiotherapy |
| NCT00003667 | Phase 2 | Completed | Not reported | Randomized vincristine–doxorubicin–cyclophosphamide with dexrazoxane, with or without ImmTher, in high-risk disease |
| NCT00038142 | Phase 2 | Terminated | 46 | Same regimen as above; stopped early |
| NCT01864109 | Phase 2 | Active, not recruiting | 83 | Irinotecan and temozolomide added to alkylator-based chemotherapy in newly diagnosed disease |
Most of these trials test doxorubicin as part of a multi-drug regimen, so they show its role in standard care rather than its effect alone.
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 and primitive neuroectodermal tumour of bone |
| 36522207 | 2022 | RCT (Phase 3) | Lancet | EE2012: comparison of two chemotherapy strategies (European and US standards) in newly diagnosed Ewing sarcoma |
| 36669140 | 2023 | RCT (Phase 3) | J Clin Oncol | Ganitumab with interval-compressed chemotherapy in metastatic Ewing sarcoma |
| 23091096 | 2012 | RCT | J Clin Oncol | Interval-compressed chemotherapy for localized Ewing sarcoma |
| 37651654 | 2023 | Long-term follow-up | J Clin Oncol | Long-term outcomes of interval-compressed chemotherapy in localized disease (AEWS0031) |
| 37403815 | 2023 | Consensus guideline | Cancer | National Ewing Sarcoma Tumor Board recommendations on standard of care |
| 26304893 | 2015 | Review | J Clin Oncol | Current management and future approaches in Ewing sarcoma |
| 20152770 | 2010 | Review | Lancet Oncol | Survival improved from about 10% to about 75% for localised 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 |
| 30231396 | 2018 | Review | ASCO Educ Book | Anthracyclines form the backbone of childhood Ewing sarcoma regimens; cardiotoxicity can be predicted and prevented |
India Market Information
At least 20 valid single-ingredient doxorubicin injection registrations are recorded, and the list may be partial. Approved indication text is not recorded in the local data. Main examples:
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 67375 | Doxobin 50mg Injection | Vial of 25 ml injection | Not recorded |
| 65986 | Doxulip 20mg Injection | Vial injection | Not recorded |
| 173138 | Oncodria 50mg Injection | Vial injection | Not recorded |
| 178247 | Pegadria 50mg Injection | Vial of 25 ml injection | Not recorded |
| 168557 | Oncodox 20mg Injection | Vial injection | Not recorded |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (anthracycline, topoisomerase II inhibitor) |
| Myelosuppression Risk | High (neutropenia, thrombocytopenia, leukopenia and anaemia are listed as concerns in the data compiled) |
| Emetogenicity Classification | Moderate to high |
| Monitoring Items | Complete blood count with differential, liver function, cardiac function (cumulative dose tracking, echocardiography) |
| Handling Protection | Must follow cytotoxic drug handling regulations |
Safety Considerations
- Conditions flagged as contraindications or cautions: the data compiled list liver failure and liver disease, heart disease, cardiomyopathy, heart failure, heart conduction disease, sudden cardiac arrest, neutropenia, leukopenia, thrombocytopenia, anaemia, agranulocytosis, and active infections (including fungal infections). These come from structured drug–disease relations, not from label text, so confirm against the package insert.
- Cardiotoxicity: cumulative anthracycline heart damage requires cardiac monitoring and dose caps. Dexrazoxane was used for cardioprotection in some Ewing sarcoma trials above.
- Drug interactions: 665 interactions are recorded. Major-level examples include dolasetron, cisapride and papaverine. Moderate-level examples include ondansetron, granisetron, palonosetron, aprepitant, dexamethasone, clarithromycin and levofloxacin; several are common antiemetics, so co-prescribing needs review.
- Secondary malignancy: topoisomerase II inhibitors are linked to therapy-related acute myeloid leukaemia in the published literature.
Package insert warnings and contraindications were not available in the local data. Please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Doxorubicin is already part of the standard multi-agent regimens tested in several completed Phase 3 randomized trials and published RCTs in Ewing sarcoma, so evidence is strong. Because it is always given in combination, and carries significant cardiac and marrow toxicity, use should remain within established protocols.
To proceed, the following is needed:
- Package insert warnings, contraindications and approved indications for the marketed Indian products
- Confirmation of the regimen, dose and cumulative-dose limits used in the supporting trials
- Cardiac monitoring and cardioprotection plan, especially for children and young adults
- Review of interacting medicines (antiemetics and QT-prolonging drugs) in the supportive-care plan
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.