Vinorelbine
| Evidence Level: L2 | Predicted Indications: 8 |
Table of Contents
Vinorelbine: Ewing sarcoma
One-Sentence Summary
Vinorelbine is a vinca alkaloid chemotherapy originally used to treat non-small cell lung cancer (NSCLC). The TxGNN model predicts it may be effective for Ewing sarcoma, with 3 clinical trials (two Phase 2 studies in mixed paediatric tumour populations and one ongoing cohort study) and 6 publications currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Ewing sarcoma |
| TxGNN Prediction Score | 1.0000 |
| Evidence Level | L2 |
| 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 |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Vinorelbine is a vinca alkaloid, a class that inhibits microtubule polymerisation, causing mitotic arrest and apoptosis in rapidly dividing cells. Its efficacy in NSCLC is well established, and mechanistically it may be applicable to Ewing sarcoma, a highly proliferative bone and soft tissue tumour.
Ewing sarcoma has high relapse rates, particularly in multi-metastatic disease. Low-dose (metronomic) cyclophosphamide combined with vinorelbine has shown activity in relapsed or refractory paediatric solid tumours. A 2026 review also discusses this combination as maintenance therapy and as the rationale for the international INTER-EWING-1 trial. Preclinical work shows synergy between microtubule-interfering drugs, including vinorelbine, and a PLK1 inhibitor in Ewing sarcoma cells.
Note that the clinical trials are in mixed tumour populations, so Ewing-specific results are not separated.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT00180947 | Phase 2 | Unknown | 210 | Vinorelbine plus cyclophosphamide in refractory or relapsed tumours, including Ewing tumours, rhabdomyosarcoma, osteosarcoma, neuroblastoma and medulloblastoma. Tumour-type applicability needs confirmation. |
| NCT00003234 | Phase 2 | Completed | 50 | Vinorelbine in children with recurrent or refractory malignancies. Mixed population; Ewing-specific results not separated. |
| NCT06451302 | Not applicable | Active, not recruiting | 100 | Prospective multicentre cohort of risk-stratified treatment in paediatric Ewing sarcoma in China. The role of vinorelbine cannot be confirmed from the title. |
No ANZCTR trial identifiers were found in the data compiled for this report.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 42561548 | 2026 | Systematic review | Cancer Treat Rev | Rationale for vinorelbine plus low-dose cyclophosphamide as maintenance therapy in the INTER-EWING-1 trial |
| 22633624 | 2012 | Phase II trial | Eur J Cancer | Vinorelbine plus continuous low-dose oral cyclophosphamide in relapsed or refractory paediatric and young adult solid tumours; good tolerance, with efficacy shown in rhabdomyosarcoma |
| 12115359 | 2002 | Phase II trial | Cancer | Vinorelbine in previously treated advanced childhood sarcomas; activity in rhabdomyosarcoma |
| 37637411 | 2023 | Review | Front Pharmacol | Review of chemotherapy for soft tissue sarcomas |
| 26260582 | 2016 | Preclinical | Int J Cancer | Synergistic apoptosis with a PLK1 inhibitor and microtubule-interfering drugs, including vinorelbine, in Ewing sarcoma cells |
| 36451163 | 2022 | Case report | BMC Urol | Extraosseous Ewing sarcoma of the kidney; diagnostic focus |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 4620E | Vinorelbine Ebewe | Solution for I.V. infusion, 50 mg (as tartrate) in 5 mL | Not available in the data compiled for this report |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (vinca alkaloid, antimicrotubule agent) |
| Myelosuppression Risk | High. Neutropenia is the dose-limiting toxicity, and leukopenia appears in the knowledge-graph contraindications. |
| Emetogenicity Classification | Low to moderate |
| Monitoring Items | Full blood count with differential, liver function, and monitoring for pulmonary symptoms and constipation or ileus |
| Handling Protection | Must follow cytotoxic drug handling regulations; intravenous use only |
Please also refer to the Product Information (PI) warnings and precautions.
Safety Considerations
- Contraindications (associations the TxGNN model (deep learning) learned between related diseases, not label text and not biological evidence): liver failure, infectious disease, ileus, intestinal obstruction, interstitial lung disease, lung disease and leukopenia.
- Drug Interactions: 100 interactions were identified in total, and the main ones from the data compiled for this report are listed below.
- Major: clarithromycin.
- Moderate: aprepitant, dexamethasone, metronidazole, eliglustat, miconazole, rolapitant, rosuvastatin, simvastatin, tinidazole and glycerol phenylbutyrate.
- Minor: levofloxacin.
Package insert warnings and contraindications for the Australian product were not available. Please refer to the TGA-approved Product Information (PI) for full safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Vinorelbine has an established role in NSCLC, a plausible antimitotic mechanism, and Phase 2 data in relapsed or refractory paediatric solid tumours, including combination use with low-dose cyclophosphamide that is being considered in the INTER-EWING-1 trial. However, the trials are in mixed populations and Ewing-specific efficacy is not yet separated, so the evidence level is L2 and use should remain within a research or specialist setting.
To proceed, the following is needed:
- Ewing sarcoma-specific results from the mixed-population Phase 2 trials (NCT00180947, NCT00003234) and the outcome of INTER-EWING-1
- Detailed mechanism of action data (MOA) and the TGA Product Information, including approved indications, warnings and contraindications
- A paediatric-specific safety and dosing plan, including myelosuppression monitoring and management of the major interaction with clarithromycin
- Confirmation of route and formulation suitability, noting that the Australian listing is an intravenous solution only
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.