Vandetanib

Evidence Level: L3

Predicted Indications: 10

Vandetanib

Pharmacist Assessment Report

Vandetanib: Renal cell carcinoma (disease)

One-Sentence Summary

Vandetanib is an oral multi-target kinase inhibitor that blocks VEGFR2, EGFR and RET. The TxGNN model predicts it may be effective for renal cell carcinoma (disease). This direction is supported by 4 clinical trials (all Phase 1/2 or Phase 2, two terminated early with very few patients) and 5 publications, none of which show vandetanib efficacy in renal cell carcinoma. Evidence level: L3.

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
India Market Status	Listed in a compiled Indian medicine price dataset (1 of 1) – CDSCO approval status is not included in this data
Number of Listed Products	1 (valid: 1)
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Vandetanib inhibits the VEGFR2, EGFR and RET tyrosine kinases. Detailed mechanism-of-action data were not available in the data compiled for this report, so the description above comes from the trial and literature records.

Clear cell renal cell carcinoma is often driven by loss of the VHL gene. This stabilises HIF and drives VEGF-dependent blood vessel growth. Blocking VEGFR2 targets this pathway directly. Approved VEGFR inhibitors such as sunitinib and pazopanib already validate the pathway in renal cell carcinoma. Rarer subtypes (FH-deficient and SDH-deficient tumours) may also respond to combined anti-angiogenic and EGFR-targeted therapy.

The caveat is that the trials are small, two were terminated early, and no efficacy results are provided in the data compiled for this report. The mechanistic rationale is plausible but unproven for vandetanib itself.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00566995	Phase 2	Completed	37	Vandetanib in von Hippel-Lindau disease with renal tumours; mechanistically well aligned, no outcome data provided
NCT02495103	Phase 1/2	Terminated	7	Vandetanib plus metformin in HLRCC- or SDH-associated kidney cancer or papillary renal cell carcinoma; hypothesis-generating only
NCT01372813	Phase 2	Terminated	3	Vandetanib in advanced clear cell renal carcinoma; too few patients to interpret
NCT01191892	Phase 2	Completed	82	Carboplatin and gemcitabine with or without vandetanib in advanced urothelial cancer; only indirectly relevant to renal cell carcinoma

Literature Evidence

PMID	Year	Type	Journal	Key Findings
40779213	2025	Review	Clin Exp Metastasis	Targeted and epigenetic approaches in metastatic FH-deficient renal cell carcinoma; several Phase 2 combination trials under way
24451769	2012	Review	Am Soc Clin Oncol Educ Book	Systemic therapy for advanced thyroid cancers, including vandetanib as a RET inhibitor
26677336	2015	Review	OncoTargets Ther	Anti-angiogenic agents in solid tumours, including vandetanib
42107510	2026	Review	Pharmacol Res	RET kinase inhibitors in RET-driven thyroid and lung cancer
31043488	2019	Preclinical (mouse model)	Mol Cancer Res	TFE3 translocation renal cell carcinoma mouse model; tangentially relevant

India Market Information

Authorization Number	Product Name	Dosage Form	Approved Indication
38486	Caprelsa Tablet (AstraZeneca)	Bottle of 30 tablets (oral)	Indication text not provided

Cytotoxicity

Item	Content
Cytotoxicity Classification	Targeted therapy (multi-target tyrosine kinase inhibitor)
Myelosuppression Risk	Please refer to the package insert warnings and precautions
Emetogenicity Classification	Please refer to the package insert warnings and precautions
Monitoring Items	Electrocardiogram (QT interval), electrolytes (potassium, calcium, magnesium), thyroid function, blood pressure, liver and renal function
Handling Protection	Please refer to the package insert warnings and precautions

Safety Considerations

Conditions listed as contraindications or cautions in the drug-disease records: hypertension, long QT syndrome (including familial forms), torsades de pointes, hypothyroidism, potassium deficiency, hypercalcaemia, impaired renal function, interstitial lung disease, heart failure, brain ischaemia or transient ischaemic attack, and posterior leukoencephalopathy syndrome. These are not taken from label text.
Drug interactions: 296 interactions were found. Major-level ones include clarithromycin, levofloxacin, dolasetron, palonosetron, picosulfuric acid, sodium sulfate and polyethylene glycol with electrolytes. Moderate-level ones include famotidine, metformin, loperamide, dexamethasone, bisacodyl and lactitol. The major interactions are mostly QT-prolonging drugs or agents that shift electrolytes, which matters because vandetanib itself prolongs the QT interval.
Class-level safety literature: meta-analyses of VEGFR inhibitors report liver toxicity, proteinuria and treatment-related mortality (PMIDs 23981115, 32105149, 22651902).

Package insert warnings and contraindications were not available; please refer to the package insert.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: The strongest support is one completed Phase 2 trial in von Hippel-Lindau disease with renal tumours (NCT00566995). The other renal cell carcinoma trials were terminated early with very few patients, and no efficacy results are available. The mechanism is plausible, but the evidence supports further research only, not clinical use.

To proceed, the following is needed:

Results from NCT00566995 and the other renal trials
Package insert warnings and contraindications, with a cardiac (QT) and electrolyte monitoring plan
Detailed mechanism-of-action data
A properly powered Phase 2 study in clear cell renal cell carcinoma or VHL-associated tumours

Disclaimer

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