Vandetanib
| Evidence Level: L3 | Predicted Indications: 10 |
Table of Contents
Vandetanib: Renal cell carcinoma (disease)
One-Sentence Summary
Vandetanib is an oral multi-target tyrosine kinase inhibitor that is already marketed in Canada. The TxGNN model predicts it may be useful for renal cell carcinoma. Four clinical trials (all Phase 1 or 2, two of them terminated early with very few patients) and a small body of mostly indirect literature currently relate to this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Renal cell carcinoma (disease) |
| TxGNN Prediction Score | 0.9992 |
| Evidence Level | L3 |
| Canada Market Status | Marketed (marketed DINs: 2 of 2) |
| Number of DINs | 2 (marketed: 2) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Vandetanib blocks VEGFR2, RET and EGFR. Detailed mechanism-of-action data were not available in the data compiled for this report, so this description relies on the target profile reported in the evidence review.
Clear cell renal cell carcinoma is typically driven by loss of the VHL gene. This leads to HIF and VEGF activation and a tumour that depends heavily on new blood vessel growth. Blocking VEGFR2 is therefore biologically plausible. Other VEGFR-targeting kinase inhibitors are already used in kidney cancer, as noted in the reviews listed below.
The clinical evidence is thin. A completed Phase 2 trial exists in von Hippel-Lindau (VHL) disease with renal tumours, and that is the main reason for the L3 rating. The other renal cancer trials were terminated early with very few patients, and no efficacy results were available to us.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00566995 | Phase 2 | Completed | 37 | Vandetanib (ZD6474) in VHL disease with renal tumours. Most relevant trial. No results were available. |
| NCT01372813 | Phase 2 | Terminated | 3 | Vandetanib in advanced clear cell renal carcinoma. Stopped after 3 patients, so no efficacy conclusion is possible. |
| NCT02495103 | Phase 1/2 | Terminated | 7 | Vandetanib plus metformin in HLRCC- or SDH-associated kidney cancer or sporadic papillary RCC. Terminated with 7 patients. |
| NCT01191892 | Phase 2 | Completed | 82 | Randomized trial of carboplatin and gemcitabine with or without vandetanib. The population appears to be urothelial cancer, so it is only indirectly relevant. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 40779213 | 2025 | Review | Clin Exp Metastasis | Targeted options for metastatic fumarate hydratase-deficient RCC. No standard regimen exists, and several Phase 2 trials of targeted combinations are under way. |
| 26677336 | 2015 | Review | OncoTargets Ther | Anti-angiogenic kinase inhibitors, including vandetanib, and their role in solid tumours. Background on the mechanism. |
| 31043488 | 2019 | Preclinical (mouse model) | Mol Cancer Res | TFE3 translocation RCC mouse model identifying possible therapeutic targets. Does not test vandetanib. |
No publication in the data compiled for this report shows that vandetanib works in renal cell carcinoma.
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02378590 | CAPRELSA | Not specified | Not specified |
| 02378582 | CAPRELSA | Not specified | Not specified |
Both licences are single-ingredient products and both are currently valid.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (multi-target tyrosine kinase inhibitor), not a conventional cytotoxic agent |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Please refer to the package insert; the class safety data below point to liver function, urine protein and ECG/QT monitoring |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
- Class-level safety signals (from literature): Meta-analyses of VEGFR-targeting kinase inhibitors report hepatic toxicity (PMID 23981115), proteinuria (PMID 32105149) and treatment-related mortality (PMID 22651902). Photosensitivity is also described for this drug class (PMID 30519172). QT prolongation is a recognised concern for vandetanib in the evidence reviewed.
- Drug Interactions: 100 interactions were identified, and 20 are shown in the data compiled for this report. The following are rated Major:
- Clarithromycin
- Levofloxacin
- Dolasetron
- Palonosetron
- Picosulfuric acid
- Polyethylene glycol 3350 with electrolytes
- Sodium sulfate
Several Moderate interactions are also listed, including metformin, famotidine, loperamide, dexamethasone, bisacodyl and lactitol. The listed Minor interactions include several proton pump inhibitors and H2 blockers.
Package insert warnings and contraindications were not available in the data compiled for this report. Please refer to the package insert for them.
Conclusion and Next Steps
Decision: Hold
Rationale: The evidence level is L3. Only one directly relevant trial was completed (Phase 2, 37 patients with VHL-associated renal tumours), and no results were available. The other renal cancer trials were terminated after 3 and 7 patients. Meanwhile, the drug carries known QT, liver and other class-related safety concerns, and many Major interactions.
To proceed, the following is needed:
- Published results of NCT00566995 (response rate, progression-free survival, safety)
- Package insert warnings and contraindications from Health Canada
- Detailed mechanism-of-action data
- A comparison of vandetanib with kinase inhibitors already established in kidney cancer
- An ECG/QT, liver function and urine protein monitoring plan, plus a review of co-medications for Major interactions
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.