Mitoxantrone
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Mitoxantrone: From Acute Myeloid Leukaemia to Upper Aerodigestive Tract Neoplasm
One-Sentence Summary
Mitoxantrone is a cytotoxic anthracenedione originally used for acute myeloid leukaemia (AML) and related myeloid leukaemias. The TxGNN model predicts it may be effective for upper aerodigestive tract neoplasm, but no clinical trials are registered under this exact term and the literature is indirect (mostly head and neck cancer, nasopharyngeal and salivary gland studies). The evidence for this specific prediction is therefore weak, although the closely related indication head and neck cancer has much stronger support (see below).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Myeloid leukaemia / acute myeloid leukaemia (the Singapore licence record contains no approved indication text) |
| Predicted New Indication | Upper aerodigestive tract neoplasm |
| TxGNN Prediction Score | 99.78% |
| Evidence Level | L4 |
| 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 information, mitoxantrone is an anthraquinone antineoplastic agent that is structurally similar to doxorubicin and acts like the anthracyclines. It works as a topoisomerase II inhibitor and DNA intercalator, causing DNA damage in rapidly dividing cells. Its efficacy in acute myeloid leukaemia is established, and mechanistically it may be applicable to other cancers.
Older studies reported some activity in head and neck cancer. Phase II studies in head and neck squamous cell carcinoma and adenoid cystic carcinoma showed limited activity, and a small series combining mitoxantrone with cisplatin in salivary gland malignancies is also available. Studies in nasopharyngeal carcinoma, including a pharmacokinetic study and a multicentre Southeast Asian phase II trial, add indirect support. Overall, the evidence is indirect and heterogeneous, and the prediction remains largely computational.
Clinical Trial Evidence
Currently no related clinical trials are registered under "upper aerodigestive tract neoplasm".
For reference, the closely overlapping indication head and neck cancer has these registered trials:
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT04902027 | Phase 1 | Completed | 45 | Liposomal mitoxantrone in recurrent/metastatic head and neck cancers (safety and efficacy) |
| NCT05717764 | Phase 3 | Not yet recruiting | 500 | Liposomal mitoxantrone + capecitabine vs capecitabine alone in recurrent metastatic nasopharyngeal carcinoma |
| NCT06472713 | Phase 2 | Recruiting | 32 | Liposomal mitoxantrone + PD-1 blockade in previously treated recurrent/metastatic nasopharyngeal carcinoma |
| NCT06892431 | Phase 2 | Not yet recruiting | 150 | JMT101 + liposomal mitoxantrone in nasopharyngeal cancer after at least two prior lines |
| NCT07070479 | Phase 2 | Recruiting | 208 | Bayesian adaptive trial of four regimens, including liposomal mitoxantrone + anti-PD-1, in PD-1-resistant nasopharyngeal carcinoma |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 1735075 | 1992 | Clinical PK/PD study | Cancer | Pharmacokinetics and pharmacodynamics of mitoxantrone in 15 patients with advanced nasopharyngeal carcinoma |
| 8418245 | 1993 | Phase II trial | J Clin Oncol | Multicentre Southeast Asian phase II trial of mitoxantrone in advanced nasopharyngeal carcinoma |
| 12045460 | 2002 | Phase II study | Anti-Cancer Drugs | Mitoxantrone + cisplatin in 14 patients with recurrent/metastatic salivary gland malignancies |
| 8922205 | 1996 | Phase II trial | Ann Oncol | EORTC phase II study in adenoid cystic carcinomas of the head and neck |
| 1650529 | 1991 | Phase II trial | Am J Clin Oncol | 19 patients with incurable head and neck carcinoma treated with mitoxantrone |
| 39952083 | 2025 | Phase 1b study | Oral Oncol | Liposomal mitoxantrone in recurrent/metastatic head and neck squamous cell carcinoma |
| 31324333 | 2019 | Systematic review | Bull Cancer | Systemic treatments for adenoid cystic carcinoma of the head and neck |
| 3512224 | 1986 | Review | Drug Intell Clin Pharm | Overview of mitoxantrone, noting some activity in head and neck cancer |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN11629P | MITOXANTRONE BAXTER INJECTION 2 mg/ml | Injection | Not stated in the available record |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (anthracenedione, topoisomerase II inhibitor) |
| Myelosuppression Risk | High (leukopenia is a dose-limiting effect in the head and neck trials; neutropenia, thrombocytopenia and anaemia appear in the knowledge-graph contraindication signals) |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Complete blood count with differential, liver function, cardiac function (cumulative dose and cardiotoxicity) |
| Handling Protection | Must follow cytotoxic drug handling regulations |
Safety Considerations
- Contraindication signals (knowledge-graph derived, not label text): liver failure, liver disease, thrombocytopenia, neutropenia, agranulocytosis, anaemia, leukopenia, heart failure, infectious disease, fungal infection, dermatophytosis, epilepsy and gallbladder disease.
- Drug Interactions: 100 interactions were identified. The main ones with a defined severity are:
- Major: dolasetron
- Moderate: clarithromycin, eliglustat, rolapitant
- Minor: levofloxacin
Many others have no severity grade assigned.
- Cardiotoxicity and cumulative anthracenedione dose should be watched, as noted for the head and neck indication.
The Singapore package insert warnings and contraindications were not available for this report. Please refer to the package insert for authoritative safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction for upper aerodigestive tract neoplasm rests on a high model score and indirect evidence only, with no registered trials under this term. Evidence is at level L4. Older single-agent studies showed limited activity. Recent liposomal mitoxantrone trials in head and neck and nasopharyngeal cancer are promising, but they involve a different formulation from the marketed Singapore injection and have no completed Phase 3 results.
To proceed, the following is needed:
- Singapore package insert warnings and contraindications (a blocking data gap)
- Mechanism of action data from DrugBank
- Results of the ongoing head and neck and nasopharyngeal carcinoma trials, especially the Phase 3 trial NCT05717764
- A decision on whether to pursue the better-supported head and neck cancer indication (evidence level L2, assessed as "Proceed with Guardrails") instead, with attention to cardiotoxicity and cumulative dose
- Evaluation of whether the conventional injection formulation is appropriate, given that the recent evidence is for the liposomal form
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.