Daunorubicin
| Evidence Level: L3 | Predicted Indications: 10 |
Table of Contents
Daunorubicin: From Acute Leukaemia to Hodgkin's Lymphoma
One-Sentence Summary
Daunorubicin is an anthracycline chemotherapy drug originally used to treat acute lymphoblastic and acute myeloid leukaemia. The TxGNN model predicts it may be effective for Hodgkin's lymphoma, but support is limited: 2 Phase 2 clinical trials (neither isolates daunorubicin) and 20 publications (mostly reviews and studies of related lymphomas) are currently available.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Acute lymphoblastic leukaemia and acute myeloid leukaemia (from the knowledge graph; the Singapore licence record contains no indication text) |
| Predicted New Indication | Hodgkin's lymphoma |
| TxGNN Prediction Score | 99.81% |
| Evidence Level | L3 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
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. This is the same mechanism as doxorubicin, which is a backbone of Hodgkin lymphoma regimens such as ABVD.
Its efficacy in leukaemia is established. Leukaemia and lymphoma are both lymphohaematopoietic malignancies, and anthracyclines are well established in lymphoid cancers. This makes the prediction plausible at the drug-class level.
The caveat is that the available trials are multi-agent Phase 2 studies that do not separate daunorubicin's contribution. Reviews note that standard first-line therapy for advanced Hodgkin's lymphoma is ABVD, which uses doxorubicin rather than daunorubicin. The evidence is therefore indirect.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00002471 | Phase 2 | Completed | Not reported | Intensive short-course combination chemotherapy for poor-risk non-lymphoblastic lymphoma, acute B-lymphoblastic leukaemia and recurrent non-Hodgkin's lymphoma; daunorubicin's contribution cannot be separated |
| NCT00002691 | Phase 2 | Completed | Not reported | LSA5 protocol for advanced paediatric and adolescent non-Hodgkin's lymphoma; a different lymphoma type, so only indirectly relevant |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 17610809 | 2007 | Systematic Review | Health Technol Assess | Cardioprotection against anthracycline toxicity in children with cancer |
| 30231396 | 2018 | Review | ASCO Educ Book | Anthracyclines (including daunorubicin) are the backbone of regimens for childhood leukaemia and Hodgkin lymphoma; cardiotoxicity is the main limitation |
| 9769779 | 1998 | Review | Jpn J Clin Oncol | Age-related pharmacokinetic changes of daunorubicin and other chemotherapy in the elderly |
| 378369 | 1979 | Review | Cancer Treat Rep | Roles and limitations of daunorubicin and adriamycin in cancer treatment |
| 14584273 | 2003 | Review (haematologic tumours) | Gan To Kagaku Ryoho | ABVD is the first-line chemotherapy for advanced Hodgkin's lymphoma; daunorubicin helped make AML curable |
| 11699226 | 2001 | Clinical study | Leuk Lymphoma | Liposomal daunorubicin in COP-X for poor-prognosis non-Hodgkin's lymphoma: 81% response (26 of 32 evaluable patients) |
| 9387047 | 1997 | Clinical study | Invest New Drugs | Liposomal daunorubicin in 19 patients with relapsed/refractory lymphoma; responses seen at the higher dose |
| 11398876 | 2001 | Clinical study | Ann Oncol | Liposomal daunorubicin in relapsed/refractory non-Hodgkin's lymphoma |
| 12688316 | 2003 | Clinical study | Leuk Lymphoma | Liposomal daunorubicin in the PVABEC regimen for 35 elderly patients with aggressive non-Hodgkin's lymphoma |
| 3855571 | 1985 | Clinical study | Scand J Haematol | Intermediate-dose cytarabine with m-AMSA or daunorubicin for relapsed acute leukaemia and lymphoblastic non-Hodgkin's lymphoma |
Note: none of these publications directly tests daunorubicin in Hodgkin's lymphoma. Most relate to non-Hodgkin's lymphoma or are general anthracycline reviews.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN11002P | DAUNOCIN FOR INJECTION 20 mg/vial | Injection, powder, for solution | Not stated in the licence record |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (anthracycline; DNA intercalator and topoisomerase II inhibitor) |
| Myelosuppression Risk | High (severe myelosuppression is a recognised effect of anthracyclines; the knowledge graph also flags neutropenia as a contraindicating condition) |
| Emetogenicity Classification | Moderate |
| Monitoring Items | Complete blood count with differential, liver and renal function, cardiac function (cardiotoxicity is the main limitation of anthracyclines) |
| Handling Protection | Must follow cytotoxic drug handling regulations |
Safety Considerations
- Contraindication-related conditions (knowledge graph, not label text): The knowledge graph links daunorubicin to caution in neutropenia and agranulocytosis, kidney disease, liver disease, cardiomyopathy, heart conduction disease and ventricular tachycardia, sudden cardiac arrest, and infectious disease (including fungal infection). These are graph associations and need confirmation against the package insert.
- Drug Interactions: 100 interactions were identified. Major-level examples include cisapride, dolasetron, papaverine, deferiprone and macimorelin. Moderate-level examples include clarithromycin, levofloxacin, ondansetron, granisetron, palonosetron and famotidine. Several of these relate to QT prolongation, which is relevant given the cardiac concerns.
Please also refer to the package insert for full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The mechanism is plausible and anthracyclines are established in lymphoid cancers. However, no trial or publication tests daunorubicin in Hodgkin's lymphoma, and the standard regimen (ABVD) already uses doxorubicin. This is a research question rather than an actionable repurposing candidate.
To proceed, the following is needed:
- Package insert warnings and contraindications from the HSA, including the approved indication text
- Mechanism of action data from DrugBank
- Direct evidence of daunorubicin in Hodgkin's lymphoma, such as comparative data against doxorubicin
- A cardiac and haematological safety monitoring plan, with review of the interacting drugs
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.