Mitoxantrone
| Evidence Level: L5 | Predicted Indications: 8 |
Table of Contents
Mitoxantrone: From Acute Myeloid Leukaemia to Head and Neck Cancer
One-Sentence Summary
Mitoxantrone is a cytotoxic anthracenedione chemotherapy agent, originally used for acute myeloid leukaemia (AML) and related myeloid disorders. The TxGNN model predicts it may be effective for upper aerodigestive tract neoplasm (highest score). The best-supported candidate in the data compiled for this report is head and neck cancer, with 6 clinical trials and 20 publications supporting that direction. Evidence for the top-ranked prediction itself is limited to 19 publications (no registered trials), mostly small phase II studies and pharmacokinetic work.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Acute myeloid leukaemia and related subtypes (from the knowledge graph; no approved indication text is available in the New Zealand licence records) |
| Predicted New Indication | Upper aerodigestive tract neoplasm (rank 1); head and neck cancer (rank 7) has the strongest evidence |
| TxGNN Prediction Score | 99.78% (upper aerodigestive tract neoplasm) |
| Evidence Level | L3 for the top prediction (observational and small phase II studies). Head and neck cancer is rated L1 in the compiled data, but this reflects a registered, not-yet-recruiting phase III trial rather than completed phase III results, so it should be read cautiously |
| New Zealand Market Status | ✗ Cancelled only |
| Number of Authorizations | 2 (both cancelled) |
| Recommended Decision | Proceed with Guardrails (head and neck cancer, as a research direction) |
Why is This Prediction Reasonable?
Mitoxantrone is a topoisomerase II inhibitor and DNA intercalator. It causes DNA damage in rapidly dividing cells and can induce immunogenic cell death. Detailed mechanism of action data is not available in the compiled drug record, but this mechanism is described in the literature, and mitoxantrone has a similar mode of action to the anthracyclines.
Its established use in AML shows activity against rapidly proliferating malignancies. Historical phase II studies also reported some activity in head and neck, salivary gland and adenoid cystic carcinomas, and in nasopharyngeal carcinoma. This provides a plausible link to upper aerodigestive tract tumours.
The evidence is uneven. Several older head and neck phase II studies showed low response rates (for example, one Southwest Oncology Group study found one partial response among 22 evaluable patients). More recent work on liposomal mitoxantrone has revived interest, including a completed phase Ib study in recurrent or metastatic head and neck cancer, active phase II studies in nasopharyngeal carcinoma, and a registered phase III trial. Immunogenic cell death induction also supports combination with PD-1 blockade.
Clinical Trial Evidence
No clinical trials are registered for the top-ranked prediction (upper aerodigestive tract neoplasm). The trials below relate to the closely related head and neck cancer prediction.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT04902027 | Phase 1 | Completed | 45 | Single-arm study of liposomal mitoxantrone in recurrent or metastatic head and neck cancer; safety and early efficacy |
| NCT05717764 | Phase 3 | Not yet recruiting | 500 | Liposomal mitoxantrone plus capecitabine vs capecitabine alone in platinum-refractory recurrent or metastatic nasopharyngeal carcinoma; no results yet |
| NCT06472713 | Phase 2 | Recruiting | 32 | Liposomal mitoxantrone plus PD-1 blockade in previously treated nasopharyngeal carcinoma |
| NCT06892431 | Phase 2 | Not yet recruiting | 150 | JMT101 (anti-EGFR antibody) plus liposomal mitoxantrone in nasopharyngeal cancer after at least two prior lines |
| NCT07070479 | Phase 2 | Recruiting | 208 | Bayesian adaptive trial of four regimens, one including liposomal mitoxantrone plus anti-PD-1, in PD-1-resistant nasopharyngeal carcinoma |
| NCT07354698 | Phase 4 | Not yet recruiting | 114 | Mitoxantrone as a lymph node tracer in robotic thyroid cancer surgery (imaging use, not antitumour therapy) |
Literature Evidence
Publications for the top-ranked prediction (upper aerodigestive tract neoplasm) and for head and neck cancer:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 39952083 | 2025 | Phase 1b | Oral Oncology | Liposomal mitoxantrone in recurrent or metastatic head and neck squamous cell carcinoma; safety and efficacy |
| 8922205 | 1996 | Phase II | Ann Oncol | EORTC phase II study in adenoid cystic carcinoma of the head and neck |
| 1650529 | 1991 | Phase II | Am J Clin Oncol | 19 patients with incurable head and neck carcinoma; dose adjusted by leukocyte nadir |
| 12045460 | 2002 | Phase II | Anti-Cancer Drugs | Mitoxantrone plus cisplatin in recurrent or metastatic salivary gland malignancies (14 patients) |
| 11290867 | 2001 | Phase II | Anti-Cancer Drugs | Ifosfamide plus mitoxantrone in recurrent or metastatic head and neck squamous cell carcinoma |
| 6511243 | 1984 | Phase II | Invest New Drugs | Southwest Oncology Group study; one partial response in 22 evaluable patients, main toxicities leukopenia and thrombocytopenia |
| 1735075 | 1992 | PK/PD study | Cancer | Pharmacokinetics and pharmacodynamics in 15 patients with advanced nasopharyngeal carcinoma |
| 34659878 | 2021 | Review | Am J Cancer Res | Systemic therapies for salivary gland adenoid cystic carcinoma |
| 31324333 | 2019 | Systematic review | Bull Cancer | Systemic treatments for metastatic or recurrent adenoid cystic carcinoma of the head and neck |
| 3512224 | 1986 | Review | Drug Intell Clin Pharm | General mitoxantrone overview; some activity reported in head and neck cancer |
New Zealand Market Information
Both New Zealand authorisations are cancelled, and no approved indication text is recorded for either.
| Authorization Number | Product Name | Dosage Form | Status |
|---|---|---|---|
| 2270463 | Mitozantrone Ebewe | Injection 2 mg/mL, 10 mL vial | Cancelled |
| 2204096 | Baxter | Injection 1 mg for ECP | Cancelled |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (anthracenedione, topoisomerase II inhibitor) |
| Myelosuppression Risk | High. Leukopenia and thrombocytopenia are the main toxicities reported in the head and neck studies |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Complete blood count with differential, liver function, renal function, and cardiac function (cardiotoxicity is described in the literature) |
| Handling Protection | Must follow cytotoxic drug handling regulations |
Safety Considerations
- Contraindications (knowledge-graph associations, not label text): liver failure, liver disease, gallbladder disease, epilepsy, heart failure, thrombocytopenia, neutropenia, agranulocytosis, leukopenia, anaemia (including macrocytic anaemia), infectious disease, fungal infectious disease, dermatophytosis. These are drug-disease links from a knowledge graph and should be verified against the official package insert.
- Drug Interactions: 355 interactions were identified in total. Major: dolasetron. Moderate: clarithromycin, eliglustat, rolapitant. Minor: levofloxacin. Many others (for example metformin, omeprazole, pantoprazole, morphine) have an unclassified severity.
- Cardiotoxicity: the literature includes a review of mitoxantrone cardiotoxicity, so cardiac monitoring is relevant.
The package insert warnings and contraindications could not be obtained for this report and should be reviewed before any further step.
Conclusion and Next Steps
Decision: Proceed with Guardrails (head and neck cancer, as a research direction only)
Rationale:
- The top-ranked prediction (upper aerodigestive tract neoplasm) rests on small, mostly older phase II studies and has no registered trials, so it is at the research-question stage. Head and neck cancer, a closely related prediction, has the most active development, including a completed phase Ib study and a registered phase III trial in nasopharyngeal carcinoma. That phase III trial has not started recruiting, so efficacy is unconfirmed.
- Both New Zealand authorisations are cancelled, and mitoxantrone carries significant myelosuppression and cardiotoxicity risks.
- Other predictions are weaker: small cell lung carcinoma (L4, Hold), well-differentiated fetal adenocarcinoma of the lung, pulmonary blastoma and bladder exstrophy complex (L5, Hold; bladder exstrophy is a congenital malformation with no plausible rationale and is likely a network artefact). Primary pulmonary lymphoma (L3) and BCR-ABL1-positive chronic myeloid leukaemia (L2, mainly blast-crisis phase II data in a field dominated by tyrosine kinase inhibitors) remain research questions.
To proceed, the following is needed:
- Medsafe package insert warnings and contraindications (a blocking gap for safety screening)
- Detailed mechanism of action data from DrugBank
- Results from the liposomal mitoxantrone phase II and III trials, noting that these use a different formulation from the conventional injection previously marketed in New Zealand
- Clarification of whether a product would be reintroduced, given the cancelled licences, and a cardiac and haematological monitoring plan
- A comparison of mitoxantrone with current standard therapy (for example, platinum-based regimens and immunotherapy) in head and neck cancer
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.