Mitoxantrone

Evidence Level: L5

Predicted Indications: 7

Mitoxantrone

Pharmacist Assessment Report

Mitoxantrone: From Acute Myeloid Leukemia to Upper Aerodigestive Tract Neoplasm

One-Sentence Summary

Mitoxantrone is a topoisomerase II-inhibiting anthracenedione chemotherapy, originally used for acute myeloid leukemia. The TxGNN model’s top-ranked prediction is upper aerodigestive tract neoplasm, but it has no registered clinical trials and only indirect literature support. A closely related prediction, head and neck cancer (rank 7), has the strongest evidence of the eight predictions: 6 mapped trials and a published 2025 phase Ib study of liposomal mitoxantrone.

Quick Overview

Item	Content
Original Indication	Acute myeloid leukemia and related myeloid leukemias (the product licenses list no indication text)
Predicted New Indication	Upper aerodigestive tract neoplasm
TxGNN Prediction Score	0.9978
Evidence Level	L5 (preclinical, mechanistic and older phase II literature only)
India Market Status	Listed in a compiled Indian medicine price dataset (4 of 4) – CDSCO approval status is not included in this data
Number of Listed Products	4 (valid: 4)
Recommended Decision	Hold

Note: Other predictions are far better supported. Head and neck cancer is rated L1 in the underlying data, but that rating is provisional (see below). Blast-crisis chronic myeloid leukemia is rated L3. The remaining predictions (small cell lung carcinoma, primary pulmonary lymphoma, fetal adenocarcinoma of the lung, pulmonary blastoma, bladder exstrophy complex) are L4–L5 and rated Hold.

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on the literature, mitoxantrone is an anthraquinone antineoplastic agent with a mechanism similar to the anthracyclines. It acts as a topoisomerase II inhibitor and DNA intercalator, and it is used in acute leukemias.

Upper aerodigestive tract tumors (head, neck, nasopharynx, salivary gland) are chemosensitive solid tumors, so a cytotoxic DNA-damaging agent is mechanistically plausible. Older phase II studies in head and neck cancer (including nasopharyngeal carcinoma, adenoid cystic carcinoma, and salivary gland malignancy with cisplatin) reported limited single-agent activity. A high TxGNN score alone does not substitute for clinical evidence, and no registered trials are mapped to this broad category. Its evidence overlaps with the head and neck cancer entry below.

Clinical Trial Evidence

No clinical trials are registered for the top-ranked prediction. The trials below are mapped to the closely related head and neck cancer prediction.

Trial Number	Phase	Status	Enrollment	Key Findings
NCT04902027	Phase 1	Completed	45	Single-arm phase Ib of liposomal mitoxantrone in recurrent/metastatic head and neck cancer
NCT05717764	Phase 3	Not yet recruiting	500	Liposomal mitoxantrone + capecitabine vs capecitabine alone in platinum-refractory recurrent/metastatic nasopharyngeal carcinoma
NCT06472713	Phase 2	Recruiting	32	Single-arm study of liposomal mitoxantrone + PD-1 blockade in previously treated nasopharyngeal carcinoma
NCT06892431	Phase 2	Not yet recruiting	150	JMT101 + liposomal mitoxantrone in nasopharyngeal cancer after at least two prior lines (combination, so mitoxantrone’s contribution is confounded)
NCT07070479	Phase 2	Recruiting	208	Bayesian adaptive trial in PD-1-resistant nasopharyngeal carcinoma; one arm uses liposomal mitoxantrone plus anti-PD-1
NCT07354698	Phase 4	Not yet recruiting	114	Mitoxantrone for lymph node tracing in thyroid surgery (not an antitumor use)

Literature Evidence

PMID	Year	Type	Journal	Key Findings
39952083	2025	Phase 1b clinical study	Oral Oncology	Liposomal mitoxantrone in recurrent/metastatic head and neck squamous cell carcinoma (head and neck cancer prediction)
8418245	1993	Phase II (multicenter)	J Clin Oncol	Mitoxantrone in advanced nasopharyngeal carcinoma in Southeast Asia
12045460	2002	Phase II	Anti-Cancer Drugs	Mitoxantrone + cisplatin in recurrent/metastatic salivary gland malignancies (14 patients)
8922205	1996	Phase II	Ann Oncol	EORTC study of mitoxantrone in adenoid cystic carcinoma of the head and neck
11290867	2001	Phase II	Anti-Cancer Drugs	Ifosfamide + mitoxantrone in recurrent/metastatic head and neck squamous cell carcinoma
1650529	1991	Phase II	Am J Clin Oncol	Mitoxantrone in head and neck carcinoma (19 patients)
6511243	1984	Phase II	Invest New Drugs	Southwest Oncology Group study: no significant antitumor activity in advanced head and neck squamous cell carcinoma
1735075	1992	PK/PD study	Cancer	Pharmacokinetics in 15 patients with advanced nasopharyngeal carcinoma
3512224	1986	Review	Drug Intell Clin Pharm	Mitoxantrone has significant activity in breast cancer, acute leukemias and non-Hodgkin lymphoma, with some activity in head and neck cancer
36070368	2022	Preclinical	Sci Transl Med	Pharmacogenomic screen in head and neck squamous cell carcinoma patient-derived cells

India Market Information

Authorization Number	Product Name	Dosage Form	Approved Indication
144939	Mitozan 2mg Injection	Vial of 10 ml injection	Not listed
210594	Scleroxil 2mg Injection	Vial of 10 ml injection	Not listed
155772	Netalem 2mg Injection	Vial of 10 ml injection	Not listed
152457	Nitrol 20mg Injection	Vial of 10 ml injection	Not listed

All four registrations are valid single-ingredient injectable products.

Cytotoxicity

Item	Content
Cytotoxicity Classification	Conventional cytotoxic (anthracenedione, topoisomerase II inhibitor)
Myelosuppression Risk	High. Leukopenia is the dose-limiting toxicity in the head and neck trials; the knowledge-graph contraindications include neutropenia, agranulocytosis, thrombocytopenia, leukopenia and anemia
Emetogenicity Classification	Please refer to the package insert warnings and precautions
Monitoring Items	CBC with differential, liver function, cardiac function (cardiotoxicity is reported in the literature)
Handling Protection	Must follow cytotoxic drug handling regulations

Safety Considerations

Key Warnings and Contraindications: Label-based data are not available. The knowledge graph links mitoxantrone to the following conditions as contraindications: liver failure, liver disease, gallbladder disease, heart failure, epilepsy, thrombocytopenia, neutropenia, agranulocytosis, leukopenia, anemia, macrocytic anemia, infectious disease, fungal infectious disease and dermatophytosis. These are not taken from label text and must be confirmed against the package insert.
Drug Interactions: 355 interactions were identified. Major: dolasetron. Moderate: clarithromycin, eliglustat, rolapitant. Minor: levofloxacin. Many others are of unknown severity (for example metformin, lansoprazole, amphotericin B, morphine, omeprazole).

Conclusion and Next Steps

Decision: Hold

Rationale: The top-ranked prediction has no registered trials and only older, mostly negative or modest phase II literature, so evidence stays at L4 despite a 0.9978 model score. The related head and neck cancer entry is rated L1 in the data, but that rests on a phase III trial that is not yet recruiting and has no results. L2 is the more defensible level, and the liposomal formulation is not the same product as the conventional injections registered in India.

To proceed, the following is needed:

Package insert warnings and contraindications for the Indian products (currently a blocking gap)
Mechanism of action data from DrugBank
Results from the liposomal mitoxantrone nasopharyngeal and head and neck trials, particularly the phase III NCT05717764
Defined sub-indications (for example nasopharyngeal carcinoma) in place of the broad “upper aerodigestive tract neoplasm” category, with a review of overlap with the head and neck cancer entry
A decision on whether conventional mitoxantrone injection or a liposomal formulation is the relevant product
A hematologic and cardiac safety monitoring plan
Disclaimer

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