Mitoxantrone
| Evidence Level: L3 | Predicted Indications: 8 |
Table of Contents
- Mitoxantrone
- Mitoxantrone: From Established Cytotoxic Chemotherapy to Upper Aerodigestive Tract Neoplasm
Mitoxantrone: From Established Cytotoxic Chemotherapy to Upper Aerodigestive Tract Neoplasm
One-Sentence Summary
Mitoxantrone is an anthraquinone cytotoxic anticancer agent, structurally similar to doxorubicin, and marketed in the US as generic injectables. The TxGNN model predicts it may be effective for upper aerodigestive tract neoplasm, but only 1 clinical trial (which does not test mitoxantrone) and 20 publications (mostly older phase II studies, preclinical work and non-therapeutic uses) exist for this exact label. The closely related prediction, head and neck cancer (rank 7), has considerably more support, including a completed phase Ib study of liposomal mitoxantrone and one phase 3 trial that has not yet started recruiting.
Quick Overview
| Item | Content |
|---|---|
| Predicted New Indication | Upper aerodigestive tract neoplasm |
| TxGNN Prediction Score | 99.78% |
| Evidence Level | L3 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 4 (all ANDA generics) |
| Recommended Decision | Hold |
The dataset does not provide the approved indication text for any US license, so the original indication is not listed.
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the Evidence Pack. The published literature describes mitoxantrone as an anthracycline-like agent. It is a topoisomerase II inhibitor and DNA intercalator with direct cytotoxic activity. It has documented activity in breast cancer, acute leukemias and non-Hodgkin lymphoma. Its activity in head and neck tumors is described as “some” (PMID 3512224).
The upper aerodigestive tract includes the oral cavity, pharynx and larynx, and tumors there are mostly squamous cell carcinomas. Older phase II studies tested mitoxantrone in squamous cell and adenoid cystic head and neck carcinoma. Combination phase II studies were also done in salivary gland malignancies (with cisplatin) and in squamous cell carcinoma (with ifosfamide). The mechanism is therefore plausibly applicable, since it is a general cytotoxic effect on rapidly dividing tumor cells.
Direct clinical evidence, however, is limited to older single-arm phase II and pharmacokinetic studies. Several older phase II trials reported little or no antitumor activity. Newer liposomal formulations are being tested in recurrent/metastatic head and neck and nasopharyngeal cancer (see below). The high graph score on its own is not proof of benefit.
Clinical Trial Evidence
For the predicted indication (upper aerodigestive tract neoplasm):
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT06953739 | Phase 3 | Not yet recruiting | 60 | Pegaspargase + P-GEMD vs P-Gemox in untreated non-upper-aerodigestive-tract or advanced extranodal NK/T-cell lymphoma. It does not appear to involve mitoxantrone, so it provides no direct evidence. |
For the closely related prediction, head and neck cancer (rank 7):
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT05717764 | Phase 3 | Not yet recruiting | 500 | Liposomal mitoxantrone + capecitabine vs capecitabine alone in recurrent/metastatic nasopharyngeal carcinoma after platinum failure. No data yet. |
| NCT04902027 | Phase 1 | Completed | 45 | Single-arm phase Ib of liposomal mitoxantrone in recurrent/metastatic head and neck cancers. |
| NCT06472713 | Phase 2 | Recruiting | 32 | Single-arm study of liposomal mitoxantrone + PD-1 blockade in previously treated recurrent/metastatic nasopharyngeal carcinoma. |
| NCT06892431 | Phase 2 | Not yet recruiting | 150 | JMT101 + liposomal mitoxantrone in recurrent/metastatic nasopharyngeal cancer after at least two prior lines. |
| NCT07070479 | Phase 2 | Recruiting | 208 | Bayesian adaptive randomized study in PD-1-resistant nasopharyngeal carcinoma, with one arm of liposomal mitoxantrone + anti-PD-1. |
| NCT07354698 | Phase 4 | Not yet recruiting | 114 | Mitoxantrone as a lymph node tracer in transoral robotic thyroid surgery. This is a surgical-aid use, not antitumor therapy. |
Literature Evidence
No RCTs were found. Studies are ordered by relevance: reviews first, then clinical studies.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 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 | Mitoxantrone is an anthracycline-like agent with significant activity in breast cancer, acute leukemia and non-Hodgkin lymphoma. Some activity is reported in head and neck cancer. |
| 12045460 | 2002 | Phase II | Anti-Cancer Drugs | Mitoxantrone + cisplatin in 14 patients with recurrent/metastatic salivary gland carcinoma. |
| 11290867 | 2001 | Phase II | Anti-Cancer Drugs | Ifosfamide + mitoxantrone in 22 patients with recurrent/metastatic squamous cell carcinoma of the head and neck. |
| 8922205 | 1996 | Phase II | Ann Oncol | EORTC study of mitoxantrone in adenoid cystic carcinoma of the head and neck, prompted by a case report of activity. |
| 1650529 | 1991 | Phase II | Am J Clin Oncol | 19 patients with incurable head and neck carcinoma received 14 mg/m² with dose adjustment by leukocyte nadir. |
| 1735075 | 1992 | Clinical PK/PD | Cancer | Pharmacokinetics in 15 patients with advanced nasopharyngeal carcinoma, described by a three-compartment model. |
| 1985750 | 1991 | Prospective series | Cancer | Chemotherapy plus radiotherapy for anaplastic thyroid carcinoma. Patients aged 65 or older received mitoxantrone. |
| 36070368 | 2022 | Preclinical | Sci Transl Med | Pharmacogenomic screen in 56 patient-derived HNSCC cell models. |
| 39472118 | 2024 | Clinical (non-therapeutic) | Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi | Mitoxantrone as a lymph node tracer in thyroid cancer surgery (180 patients). This is an imaging use, not treatment. |
For head and neck cancer (rank 7), a 2025 phase Ib study of liposomal mitoxantrone in recurrent/metastatic HNSCC was also published (PMID 39952083, Oral Oncology). Several older single-agent phase II studies in squamous cell carcinoma (for example PMID 6511243) reported little significant antitumor activity.
US Market Information
| Authorization Number | Product Name | Dosage Form | Manufacturer |
|---|---|---|---|
| ANDA077496 | Mitoxantrone | Injection, solution | Fresenius Kabi USA, LLC |
| ANDA077356 | mitoXANTRONE | Injection, solution, concentrate | Meitheal Pharmaceuticals Inc. |
| ANDA076871 | Mitoxantrone | Injection, solution, concentrate | Hospira, Inc. |
The dataset lists ANDA077356 twice, so it is shown once here. All products are injectables. Approved indication text is not provided in the dataset.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (anthracenedione, topoisomerase II inhibitor and DNA intercalator) |
| Myelosuppression Risk | High. Leukopenia and thrombocytopenia are the major toxicities in the head and neck phase II studies, and dosing was adjusted by leukocyte nadir. |
| Emetogenicity Classification | Low to moderate |
| Monitoring Items | CBC with differential, liver function, and cardiac function (it is structurally related to doxorubicin, and cardiotoxicity has been studied) |
| Handling Protection | Must follow cytotoxic drug handling regulations |
Please refer to the package insert warnings and precautions for full details.
Safety Considerations
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: For the exact label “upper aerodigestive tract neoplasm,” the only registered trial does not test mitoxantrone, and the clinical literature is limited to older phase II studies with modest or negative results. The evidence is only at L3, and the package insert safety data needed for screening is missing. The related head and neck cancer prediction is more promising (L2). Liposomal formulations have a completed phase Ib study, several phase 2 studies and one phase 3 trial that has not yet started recruiting, but none has reported efficacy results yet.
To proceed, the following is needed:
- Package insert warnings and contraindications (a blocking gap for safety screening)
- DrugBank mechanism of action data
- Results from the liposomal mitoxantrone trials (NCT04902027, NCT05717764, NCT06472713)
- A decision on whether to pursue the standard injectable or the liposomal formulation, since the newer trials use the liposomal one
- A cardiac and hematologic monitoring plan
This report is for research reference only and does not constitute medical advice. Repurposing candidates require clinical validation before use.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.