Vandetanib
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
Vandetanib: From Medullary Thyroid Cancer to Renal Cell Carcinoma
One-Sentence Summary
Vandetanib is a multi-targeted tyrosine kinase inhibitor (VEGFR2/3, EGFR, RET) originally used to treat advanced medullary thyroid cancer. The TxGNN model predicts it may be effective for Renal Cell Carcinoma, with 4 clinical trials and 6 publications currently supporting this direction — though most trials are small, terminated, or Phase 2 only.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Medullary Thyroid Cancer (per literature evidence; not formally captured in structured original_indications) |
| Predicted New Indication | Renal Cell Carcinoma |
| TxGNN Prediction Score | 99.92% |
| Evidence Level | L2 |
| India Market Status | ✗ Not Marketed |
| Number of Registrations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Vandetanib is a multi-target tyrosine kinase inhibitor with activity against VEGFR2/3, EGFR, and RET. Its approved use in medullary thyroid cancer is driven primarily by RET pathway inhibition (constitutively activated RET kinase in MTC). Structured mechanism-of-action data was not available in DrugBank for this Evidence Pack, so the MOA description above is reconstructed from the literature and predicted-indication rationale fields supplied in the pack rather than a formal original_moa record.
Renal cell carcinoma — particularly Von Hippel-Lindau (VHL)-associated and clear cell subtypes — is a prototypically angiogenesis-dependent tumor, driven by the VHL-HIF-VEGF axis. Because vandetanib’s VEGFR2 inhibitory activity is a core part of its pharmacology (independent of its RET activity in MTC), there is a direct mechanistic rationale for activity in VEGF-driven RCC subtypes, even though the two cancers are unrelated by tissue origin.
This mechanistic plausibility is reflected in the trial record: the strongest single study (NCT00566995) specifically enrolled patients with VHL disease and renal tumors, directly testing the VEGFR-inhibition hypothesis. However, several other RCC-labeled trials in this Evidence Pack (e.g., NCT01191892, using a carboplatin+gemcitabine backbone) appear to actually target urothelial/transitional cell carcinoma rather than renal cell carcinoma, suggesting a possible disease-label mismatch that should be verified before relying on aggregate trial counts.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00566995 | Phase 2 | Completed | 37 | Tested vandetanib in VHL disease and renal tumors; directly probes VEGFR-driven RCC biology (Grade A relevance). |
| NCT01191892 | Phase 2 | Completed | 82 | Randomized carboplatin+gemcitabine ± vandetanib in cisplatin-ineligible advanced urothelial cancer; chemo backbone suggests this is urothelial, not RCC, cancer — disease label likely mismatched (Grade C). |
| NCT02495103 | Phase 1/2 | Terminated | 7 | Vandetanib + metformin in HLRCC/SDH-associated kidney cancer or sporadic papillary RCC; terminated early, very small n. |
| NCT01372813 | Phase 2 | Terminated | 3 | Vandetanib monotherapy in advanced clear cell RCC; terminated with only 3 patients enrolled — hypothesis-generating only. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 40779213 | 2025 | Review | Clinical & Experimental Metastasis | Discusses targeted therapy combinations under evaluation for fumarate hydratase-deficient RCC, a molecularly defined RCC subtype with no established standard regimen. |
| 26677336 | 2015 | Review | OncoTargets and Therapy | Reviews antiangiogenic TKIs (including vandetanib) approved across solid tumor types, framing the VEGFR-inhibition rationale for angiogenesis-dependent cancers. |
| 28477875 | 2017 | Review | Bulletin du Cancer | Reviews cabozantinib (VEGFR2/MET/RET inhibitor) MOA and efficacy, providing class-level context for RET/VEGFR-targeted agents like vandetanib. |
| 24451769 | 2012 | Review | ASCO Educational Book | Confirms vandetanib’s FDA approval for RET-driven medullary thyroid cancer — the drug’s established original indication. |
| 36302175 | 2023 | Trial (different drug) | Clinical Cancer Research | Phase 2 trial of guadecitabine (not vandetanib) in SDH-deficient tumors including HLRCC-associated RCC; relevant disease context but not direct vandetanib evidence. |
| 31043488 | 2019 | Preclinical/Animal Model | Molecular Cancer Research | Mouse model of TFE3 translocation RCC identifying novel therapeutic targets and a diagnostic biomarker (GPNMB); does not test vandetanib directly. |
India Market Information
Vandetanib is not currently marketed in India (0 registrations, market status: not marketed). No authorization records are available for review.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (multi-target tyrosine kinase inhibitor: VEGFR2/3, EGFR, RET) — not a conventional cytotoxic agent |
| Myelosuppression Risk | Not directly reported in this Evidence Pack for vandetanib specifically; please refer to the package insert warnings and precautions |
| Emetogenicity Classification | Not directly reported in this Evidence Pack; please refer to the package insert warnings and precautions |
| Monitoring Items | Hepatic function (class-level meta-analysis of anti-angiogenic TKI hepatotoxicity, PMID 23981115) and renal function/urinalysis for proteinuria (class-level VEGFR-TKI meta-analysis, PMID 32105149) |
| Handling Protection | No vandetanib-specific handling data in this pack; as an oral antineoplastic agent, follow institutional hazardous-drug handling protocols pending confirmation |
Safety Considerations
Drug Interactions (296 total interactions on file; sample below):
| Interacting Drug | Severity |
|---|---|
| Clarithromycin | Major |
| Picosulfuric acid | Major |
| Polyethylene glycol (3350 with electrolytes) | Major |
| Dolasetron | Major |
| Palonosetron | Major |
| Sodium sulfate | Major |
| Levofloxacin | Major |
| Famotidine | Moderate |
| Metformin | Moderate |
| Loperamide | Moderate |
| Dexamethasone | Moderate |
| Bisacodyl | Moderate |
| Lactitol | Moderate |
Minor-level interactions (Ranitidine, Rabeprazole, Dexlansoprazole, Naloxegol, Lansoprazole, Metronidazole, Omeprazole) are also on file but generally require no action.
No structured key warnings or contraindications are currently available — please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: A blocking data gap exists on India-specific labeling (warnings/contraindications), which prevents completion of the S1 safety assessment. While the mechanistic rationale for VEGFR-driven RCC subtypes (especially VHL-associated/clear cell RCC) is sound and supported by an L2-level completed Phase 2 trial, the overall evidence base is thin — most trials are small, terminated, or possibly mislabeled — and the drug has no market presence in India.
To proceed, the following is needed:
- Resolve DG001 (India labeling/warnings/contraindications) — currently Blocking
- Resolve DG002 (formal MOA confirmation via DrugBank API)
- Verify whether NCT01191892 is correctly labeled as RCC or is actually urothelial cancer, before counting it as supporting evidence
- Prioritize confirmatory studies in VHL-associated/clear cell RCC specifically, where mechanistic and trial evidence is strongest
- Establish an India regulatory pathway assessment given current non-marketed status
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.