Daunorubicin
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
- Daunorubicin
- Pharmacist Assessment Report
- Daunorubicin: anthracycline topoisomerase II inhibitor → Hodgkins lymphoma
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- Australia Market Information
- Cytotoxicity
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Daunorubicin: anthracycline topoisomerase II inhibitor → Hodgkins lymphoma
One-Sentence Summary
Daunorubicin is an anthracycline chemotherapy agent. The TxGNN model predicts it may be useful for Hodgkins lymphoma. Evidence is thin: the 2 registered trials and most of the 19 publications concern non-Hodgkin lymphoma or general anthracycline topics, and none directly tests daunorubicin in Hodgkin lymphoma.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Hodgkins lymphoma |
| TxGNN Prediction Score | 0.9981 |
| Evidence Level | L5 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Daunorubicin is an anthracycline that intercalates into DNA and inhibits topoisomerase II. This is a plausible mechanism against lymphoid malignancies. Detailed mechanism of action data was not available in the data compiled for this report, so this description reflects general class knowledge.
Anthracyclines are widely used in lymphoma regimens, which gives a general rationale. However, the established anthracycline in Hodgkin lymphoma is doxorubicin, given within the ABVD regimen. The publications that mention Hodgkin lymphoma do so in the context of doxorubicin-based or other regimens, so the added value of daunorubicin is unclear. The trials and cohort studies found mainly address non-Hodgkin lymphoma, a different disease. Because no cited study directly examines daunorubicin in Hodgkin lymphoma, the prediction is classed as model-based only (L5).
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT00002471 | Phase 2 | Completed | Not reported | Intensive short-course combination chemotherapy in poor-risk non-lymphoblastic lymphoma, acute B-lymphoblastic leukaemia and recurrent non-Hodgkin lymphoma. Not Hodgkin-specific. |
| NCT00002691 | Phase 2 | Completed | Not reported | LSA5 combination chemotherapy protocol in advanced paediatric non-Hodgkin lymphoma. A different disease entity. |
No ANZCTR trials were identified.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 30231396 | 2018 | Review | ASCO Educational Book | Anthracyclines, including daunorubicin, form the backbone of regimens for several childhood cancers, including Hodgkin lymphoma. Cardiotoxicity limits their use. |
| 14584273 | 2003 | Review | Gan to Kagaku Ryoho | Overview of haematologic tumour chemotherapy. First-line treatment for advanced Hodgkin lymphoma is ABVD, based on a randomised comparison with MOPP. |
| 10410671 | 1999 | Review | Gan to Kagaku Ryoho | Overview of haematologic tumour chemotherapy, including standard regimens for advanced Hodgkin lymphoma. |
| 17610809 | 2007 | Systematic review | Health Technology Assessment | Technologies for reducing anthracycline cardiotoxicity in children. |
| 9769779 | 1998 | Review | Japanese Journal of Clinical Oncology | Chemotherapy in the elderly. Notes age-related pharmacokinetic changes for daunorubicin and other agents. |
| 11699226 | 2001 | Cohort | Leukemia & Lymphoma | Liposomal daunorubicin in a COP-X salvage regimen: 81% of 32 evaluable patients with non-Hodgkin lymphoma responded. |
| 9387047 | 1997 | Cohort | Investigational New Drugs | Liposomal daunorubicin in 19 patients with relapsed or refractory lymphoma. Responses were seen at the higher dose, with mild non-haematological toxicity. |
| 11398876 | 2001 | Cohort | Annals of Oncology | Liposomal daunorubicin in relapsed or refractory non-Hodgkin lymphoma. |
| 12688316 | 2003 | Cohort | Leukemia & Lymphoma | Liposomal daunorubicin within the PVABEC regimen in 35 elderly patients with aggressive non-Hodgkin lymphoma. |
| 3855571 | 1985 | Cohort | Scandinavian Journal of Haematology | Intermediate-dose cytarabine with m-AMSA or daunorubicin in 27 patients with relapsed acute leukaemia and lymphoblastic non-Hodgkin lymphoma. |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 14661P | Vyxeos | Powder for I.V. infusion containing daunorubicin 44 mg (as hydrochloride) and cytarabine 100 mg | Not recorded in the local data |
This is a fixed-combination daunorubicin and cytarabine product. It should not be taken as describing the approval or marketing of daunorubicin as a single ingredient.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (anthracycline class) |
| Myelosuppression Risk | High (neutropenia and thrombocytopenia expected with this class) |
| Emetogenicity Classification | Moderate |
| Monitoring Items | Full blood count with differential, liver and renal function, cardiac function (anthracycline cardiotoxicity) |
| Handling Protection | Must follow cytotoxic drug handling regulations |
Please also refer to the Product Information (PI) warnings and precautions.
Safety Considerations
- Drug Interactions: 387 interactions are recorded. Major-level interactions include cisapride, dolasetron, papaverine, deferiprone and macimorelin. Moderate-level interactions include ondansetron, granisetron, palonosetron, clarithromycin, levofloxacin, famotidine and loperamide.
- Cardiotoxicity: The anthracycline literature reviewed above identifies cardiotoxicity as the main limiting adverse effect.
Please refer to the TGA-approved Product Information (PI) for full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The high TxGNN score (0.9981) is not backed by any study directly testing daunorubicin in Hodgkin lymphoma. The trials found address non-Hodgkin lymphoma, and doxorubicin within ABVD is already the established anthracycline for Hodgkin lymphoma, so the incremental value of daunorubicin is unclear.
To proceed, the following is needed:
- Hodgkin lymphoma-specific clinical or preclinical data on daunorubicin, ideally compared with doxorubicin
- Mechanism of action data
- Product Information warnings and contraindications for safety screening
- Clarification of which Australian daunorubicin products exist beyond the fixed-combination product
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.