Mitoxantrone

Evidence Level: L5

Predicted Indications: 7

Mitoxantrone

Pharmacist Assessment Report

Mitoxantrone: From Acute Myeloid Leukaemia to Upper Aerodigestive Tract Neoplasm

One-Sentence Summary

Mitoxantrone is a cytotoxic anthracenedione chemotherapy, originally used for acute myeloid leukaemia (AML) and related myeloid leukaemias. The TxGNN model predicts it may be effective for upper aerodigestive tract neoplasm (top-ranked prediction), but the best-supported related prediction in the data compiled for this report is head and neck cancer, which has 6 registered clinical trials and 20 publications, mostly phase II or earlier, with a phase III trial registered but not yet recruiting.

Quick Overview

Item	Content
Original Indication	Acute myeloid leukaemia and related myeloid leukaemias (the ARTG entry does not list indication text)
Predicted New Indication	Upper aerodigestive tract neoplasm (rank 1); head and neck cancer (rank 7) is the best-evidenced prediction and is used for the evidence sections below
TxGNN Prediction Score	0.9978 (upper aerodigestive tract neoplasm); 0.9931 (head and neck cancer)
Evidence Level	L5 (upper aerodigestive tract neoplasm); L1 (head and neck cancer, as scored in the data compiled for this report)
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	Proceed with Guardrails (head and neck cancer); Hold for other predictions

Note: the L1 grade for head and neck cancer is generous. It rests on a completed phase Ib study and older phase II studies, not on completed phase 3 RCTs as the standard L1 definition requires. I would treat it as closer to L2-L3 in practice.

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 a topoisomerase II inhibitor and DNA intercalator, structurally similar to the anthracyclines. It is established in AML and other haematological malignancies, and its cytotoxic mechanism could plausibly apply to rapidly dividing squamous and glandular tumour cells.

Older single-agent phase II trials in head and neck squamous cell carcinoma showed modest or minimal activity (for example, one partial response among 22 evaluable patients in a Southwest Oncology Group study). More recent work focuses on a liposomal formulation of mitoxantrone, particularly in nasopharyngeal carcinoma, where several trials are underway.

The model’s other predictions have weaker support. Small cell lung carcinoma has only indirect or preclinical evidence. Primary pulmonary lymphoma has small retrospective data, which is plausible because mitoxantrone is used in lymphoma regimens. BCR-ABL positive chronic myeloid leukaemia is plausible only for blast crisis, since TKIs have largely replaced chemotherapy in chronic phase. Well-differentiated fetal adenocarcinoma of the lung and pulmonary blastoma have no trials or literature. The bladder exstrophy-epispadias-cloacal exstrophy complex is a congenital malformation with no plausible mechanistic link, and the score is likely a prediction artefact.

Clinical Trial Evidence

Trials below are for head and neck cancer (the best-supported prediction). The top-ranked upper aerodigestive tract neoplasm prediction has no registered trials.

Trial Number	Phase	Status	Enrolment	Key Findings
NCT04902027	Phase 1b	Completed	45	Single-arm study of mitoxantrone liposome injection in recurrent/metastatic head and neck cancer; safety and preliminary efficacy
NCT05717764	Phase 3	Not yet recruiting	500	Randomised trial of liposomal mitoxantrone plus capecitabine vs capecitabine alone in platinum-refractory recurrent/metastatic nasopharyngeal carcinoma
NCT06472713	Phase 2	Recruiting	32	Single-arm study of liposomal mitoxantrone plus PD-1 blockade in previously treated nasopharyngeal carcinoma
NCT06892431	Phase 2	Not yet recruiting	150	JMT101 plus liposomal mitoxantrone in nasopharyngeal cancer after at least two prior lines
NCT07070479	Phase 2	Recruiting	208	Bayesian adaptive trial of four regimens in PD-1-resistant nasopharyngeal carcinoma, including liposomal mitoxantrone plus anti-PD-1 (mitoxantrone is one arm of several)
NCT07354698	Phase 4	Not yet recruiting	114	Mitoxantrone used for lymphatic tracing in transoral robotic thyroid cancer surgery (imaging use, not antitumour therapy)

No ANZCTR identifiers were found in the data compiled for this report.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
39952083	2025	Phase 1b	Oral Oncology	Liposomal mitoxantrone in recurrent/metastatic head and neck squamous cell carcinoma
8922205	1996	Phase II	Ann Oncol	EORTC phase II study of mitoxantrone in adenoid cystic carcinoma of the head and neck
11290867	2001	Phase II	Anti-Cancer Drugs	Ifosfamide plus mitoxantrone in recurrent/metastatic squamous cell carcinoma of the head and neck (22 patients)
12045460	2002	Phase II	Anti-Cancer Drugs	Mitoxantrone plus cisplatin in salivary gland malignancies (14 patients)
1650529	1991	Phase II	Am J Clin Oncol	Single-agent mitoxantrone in 19 patients with head and neck carcinoma
6511239	1984	Phase II	Invest New Drugs	Phase II trial of mitoxantrone in advanced head and neck cancer
6511243	1984	Phase II	Invest New Drugs	Southwest Oncology Group study: one partial response in 22 evaluable patients; no significant activity; leukopenia and thrombocytopenia were the main toxicities
8418245	1993	Phase II	J Clin Oncol	Multicentre phase II trial in advanced nasopharyngeal carcinoma in Southeast Asia
34659878	2021	Review	Am J Cancer Res	Systemic therapies for salivary gland adenoid cystic carcinoma
31324333	2019	Systematic review	Bull Cancer	Systemic treatments for recurrent/metastatic adenoid cystic carcinoma of the head and neck

Australia Market Information

ARTG Number	Product Name	Dosage Form	Approved Indication
ARTG 4514N	Mitozantrone Ebewe	Injection 20 mg (as hydrochloride) in 10 mL	Not listed in the data compiled for this report

The available product is the conventional (non-liposomal) injection. The recent head and neck trials use a liposomal formulation, which is not among the ARTG entries listed here.

Cytotoxicity

Item	Content
Cytotoxicity Classification	Conventional cytotoxic (anthracenedione, topoisomerase II inhibitor)
Myelosuppression Risk	High (leukopenia and thrombocytopenia were the main toxicities in the head and neck phase II studies)
Emetogenicity Classification	Low to moderate
Monitoring Items	Full blood count with differential, liver function, cardiac function (cardiotoxicity is a recognised risk), and other parameters per the Product Information
Handling Protection	Must follow cytotoxic drug handling regulations

Please refer to the Product Information (PI) warnings and precautions for definitive guidance.

Safety Considerations

Contraindication-related conditions (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 and dermatophytosis. Several reflect the drug’s myelosuppressive effect.
Drug Interactions: 355 interactions were identified. Main ones:
- Major: dolasetron
- Moderate: clarithromycin, eliglustat, rolapitant
- Minor: levofloxacin
- Many others, such as metformin, amphotericin B and omeprazole, are of unknown severity.
Cardiotoxicity: noted in the literature compiled for this report and should be managed with monitoring.

Please refer to the TGA-approved Product Information (PI) for full warnings and contraindications, as label-based safety data were not available for this report.

Conclusion and Next Steps

Decision: Proceed with Guardrails (head and neck cancer only; Hold for the other predictions)

Rationale:

Head and neck cancer, particularly nasopharyngeal carcinoma, has an active liposomal mitoxantrone programme with a completed phase Ib study and a registered phase III trial. However, the phase III has not started recruiting, historical single-agent phase II results were modest, and the product available in Australia is the conventional formulation. Evidence is promising but not yet confirmatory.
Small cell lung carcinoma, well-differentiated fetal adenocarcinoma of the lung, pulmonary blastoma and bladder exstrophy complex should be held. Primary pulmonary lymphoma and BCR-ABL positive CML are better treated as research questions.

To proceed, the following is needed:

Results from the NCT05717764 phase III and the ongoing phase II studies
Clarity on whether a liposomal formulation is available or registrable in Australia, since the current ARTG entry is the conventional injection
Detailed mechanism of action data
Label-based warnings and contraindications from the TGA Product Information
A cardiac and haematological monitoring plan
Registration of any Australian trial on ANZCTR if local studies are planned
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.