Daunorubicin
| Evidence Level: L3 | Predicted Indications: 10 |
Table of Contents
Daunorubicin: From Acute Leukemia to Hodgkins lymphoma
One-Sentence Summary
Daunorubicin is an anthracycline chemotherapy drug, originally used to treat acute lymphoblastic and acute myeloid leukemia. The TxGNN model predicts it may be effective for Hodgkin’s lymphoma, but the supporting evidence is indirect: 2 Phase 2 clinical trials (both of multi-drug regimens, one in non-Hodgkin lymphoma) and a set of mostly review-type or non-Hodgkin lymphoma publications.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Acute lymphoblastic leukemia and acute myeloid leukemia (and related subtypes) |
| Predicted New Indication | Hodgkin’s lymphoma |
| TxGNN Prediction Score | 0.9981 |
| Evidence Level | L3 |
| India Market Status | Listed in a compiled Indian medicine price dataset (6 of 6) – CDSCO approval status is not included in this data |
| Number of Listed Products | 6 (valid: 6) |
| 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, daunorubicin is an anthracycline that intercalates into DNA and inhibits topoisomerase II. Its efficacy in acute leukemia is well established.
Doxorubicin, a closely related anthracycline with the same mechanism, is a backbone of Hodgkin lymphoma regimens such as ABVD. This makes it mechanistically plausible that daunorubicin could be active in Hodgkin lymphoma. Review literature also notes that anthracyclines as a class form the backbone of regimens for leukemia, Hodgkin lymphoma and several paediatric solid tumours.
However, the available trials are multi-drug studies, so daunorubicin’s own contribution cannot be separated from the other agents. The prediction should be read as a research question, not as proof of benefit.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00002471 | Phase 2 | Completed | Not reported | Intensive short-course combination chemotherapy in poor-risk nonlymphoblastic lymphoma, acute B-lymphoblastic leukemia and recurrent non-Hodgkin lymphoma; daunorubicin’s specific role unclear |
| NCT00002691 | Phase 2 | Completed | Not reported | LSA5 combination chemotherapy protocol in advanced paediatric and adolescent non-Hodgkin lymphoma (a different disease from Hodgkin lymphoma; indirect evidence) |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 30231396 | 2018 | Review | ASCO Educational Book | Anthracyclines, including daunorubicin, form the backbone of regimens for childhood leukemia and Hodgkin lymphoma; cardiotoxicity limits their use |
| 17610809 | 2007 | Systematic review | Health Technology Assessment | Methods to protect children from anthracycline cardiotoxicity |
| 378369 | 1979 | Review | Cancer Treatment Reports | Roles and limitations of daunorubicin and adriamycin in cancer treatment |
| 14584273 | 2003 | Review (narrative) | Gan To Kagaku Ryoho | ABVD is first-line for advanced Hodgkin lymphoma; daunorubicin is central to AML treatment |
| 11699226 | 2001 | Clinical study | Leukemia & Lymphoma | Liposomal daunorubicin in COP-X for poor-prognosis non-Hodgkin lymphoma: 81% response among 32 evaluable patients |
| 9387047 | 1997 | Clinical study | Investigational New Drugs | Liposomal daunorubicin in relapsed/refractory lymphoma: one complete and two partial responses at the higher dose |
| 11398876 | 2001 | Clinical study | Annals of Oncology | Liposomal daunorubicin in relapsed or refractory non-Hodgkin lymphoma |
| 8535227 | 1995 | Phase 3 trial | Leukemia & Lymphoma | CHOP vs CIOP (idarubicin) in intermediate-grade non-Hodgkin lymphoma; does not test daunorubicin |
Most of this literature concerns non-Hodgkin lymphoma or general anthracycline use, not Hodgkin lymphoma itself.
India Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 60654 | Daunomycin 20mg Injection (Pfizer Ltd) | Vial of 10 ml injection | Not stated |
| 59802 | Daunotec 20mg Injection (Cipla Ltd) | Vial of 4 ml injection | Not stated |
| 63524 | Daunorubitec Injection (United Biotech Pvt Ltd) | Vial of 1 injection | Not stated |
| 67377 | Daunocin 20mg Injection (Miracalus Pharma Pvt Ltd) | Vial of 1 powder for injection | Not stated |
| 66182 | Daunocin 20mg Injection (Vhb Life Sciences Inc) | Vial of 2 ml injection | Not stated |
A sixth licence (61794, Dauneon 20mg Injection, Neon Laboratories Ltd) is also valid. All six licences are for single-ingredient injectable products.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (anthracycline, topoisomerase II inhibitor) |
| Myelosuppression Risk | High (neutropenia is a known concern; the knowledge graph lists neutropenia and agranulocytosis as contraindicated conditions) |
| Emetogenicity Classification | Moderate |
| Monitoring Items | CBC with differential, liver and renal function, cardiac function (anthracycline cardiotoxicity) |
| Handling Protection | Must follow cytotoxic drug handling regulations |
Please refer to the package insert warnings and precautions for full details.
Safety Considerations
- Disease-level cautions (from drug-disease relationships in the knowledge graph, not label text): Conditions flagged include neutropenia and related congenital neutropenias, agranulocytosis, cardiomyopathy, heart conduction disease, ventricular tachycardia, sudden cardiac arrest, kidney disease, liver disease, gallbladder disease, epilepsy, and active infectious disease.
- Drug Interactions: 387 interactions were identified. Major-level examples include cisapride, dolasetron, papaverine, deferiprone and macimorelin. Moderate-level examples include famotidine, loperamide, clarithromycin, levofloxacin, ondansetron, granisetron and palonosetron.
- The literature also repeatedly highlights anthracycline-related cardiotoxicity.
Package insert warnings and contraindications were not available in the data compiled for this report; please refer to the package insert.
Conclusion and Next Steps
Decision: Hold
Rationale: The mechanistic rationale is plausible, and doxorubicin is already part of standard Hodgkin lymphoma regimens. However, the only trials are Phase 2 multi-drug studies, one of which is in non-Hodgkin lymphoma, and none isolates daunorubicin’s contribution in Hodgkin lymphoma. Evidence is limited to L3, and the safety profile (myelosuppression, cardiotoxicity) is substantial. Other predicted indications (for example neuroblastoma and ALK-positive large B-cell lymphoma) have similarly indirect evidence, and several have no evidence beyond the prediction score.
To proceed, the following is needed:
- Package insert warnings, contraindications and approved indications from the India registrations
- Detailed mechanism of action data
- Trials or studies testing daunorubicin specifically in Hodgkin lymphoma, with the drug composition of the multi-agent regimens confirmed
- A cardiac and haematological safety monitoring plan, including cumulative anthracycline dose limits
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.