Vandetanib
| 證據等級: L5 | 預測適應症: 10 個 |
目錄
Vandetanib: From Medullary Thyroid Cancer to Renal Cell Carcinoma
One-Sentence Summary
Vandetanib is an oral multi-kinase inhibitor (VEGFR2/3, EGFR, RET) whose established oncology use is in medullary thyroid cancer, based on evidence found in this pack’s literature set. The TxGNN model predicts it may be effective for Renal Cell Carcinoma, with 4 clinical trials and 6 publications currently supporting this direction — though two of the four trials were terminated early with very small enrollment.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Medullary Thyroid Cancer (MTC) — no formal license record on file; inferred from literature evidence (PMID 24451769, 32691271) |
| Predicted New Indication | Renal Cell Carcinoma |
| TxGNN Prediction Score | 99.92% |
| Evidence Level | L2 |
| US Market Status | Not Marketed |
| Number of NDAs | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, a formal original_moa record is not available (flagged as a High-severity data gap, DG002). Based on the mechanistic description captured in this evidence pack’s repurposing rationale, vandetanib is a multi-target tyrosine kinase inhibitor that blocks VEGFR2/3, EGFR, and RET. VEGFR2 inhibition is a well-established anti-angiogenic strategy already used in RCC treatment (e.g., sunitinib, pazopanib, cabozantinib), so vandetanib’s mechanism overlaps meaningfully with drugs already approved for this indication — a plausible “class effect” extension.
Clear cell RCC in particular is driven by VHL gene inactivation → HIF accumulation → VEGF overexpression, making it the RCC subtype with the strongest biological rationale for a VEGFR-targeted agent. This is reflected in the trial evidence: the largest completed study in this evidence set enrolled VHL-disease-associated renal tumor patients (NCT00566995, n=37).
However, mechanistic plausibility is undercut by execution: two of the four directly relevant trials were terminated with only 3 and 7 patients enrolled respectively, and the only trial with meaningful enrollment for a general RCC population (NCT01191892, n=82) was actually designed for urothelial cancer, raising disease-match uncertainty. Vandetanib itself has not demonstrated superiority over already-approved RCC TKIs in any completed trial.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00566995 | Phase 2 | Completed | 37 | Vandetanib in Von Hippel-Lindau disease and renal tumors; VEGFR2 mechanism highly relevant to VHL-driven RCC |
| NCT01372813 | Phase 2 | Terminated | 3 | Directly targeted advanced clear cell RCC; terminated after only 3 patients, feasibility/safety signal unclear |
| NCT02495103 | Phase 1/2 | Terminated | 7 | Vandetanib + metformin in HLRCC/SDH-associated or sporadic papillary RCC; terminated with limited enrollment |
| NCT01191892 | Phase 2 | Completed | 82 | Randomized carboplatin/gemcitabine ± vandetanib; designed for advanced urothelial cancer, not classic RCC — disease-match uncertain |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 22651902 | 2012 | Meta-analysis | Cancer Treat Rev | Treatment-related mortality risk across VEGFR-TKI class (including vandetanib) in solid tumors |
| 40779213 | 2025 | Review | Clin Exp Metastasis | Targeted therapy approaches in fumarate hydratase-deficient RCC; no established standard regimen |
| 32105149 | 2020 | Review/Meta-analysis | Expert Rev Clin Pharmacol | Proteinuria risk associated with VEGFR-TKIs including vandetanib |
| 23981115 | 2014 | Review/Meta-analysis | Br J Clin Pharmacol | Hepatic toxicity incidence and risk across anti-angiogenic TKIs |
| 31043488 | 2019 | Preclinical (mouse model) | Mol Cancer Res | TFE3-translocation RCC model identifies novel therapeutic targets and diagnostic marker |
| 26677336 | 2015 | Review | OncoTargets Ther | Class overview of antiangiogenic TKIs (nintedanib, sunitinib, sorafenib, pazopanib, vandetanib) in solid tumors |
US Market Information
No NDA or license records are currently on file for vandetanib in this jurisdiction (total_licenses: 0). The drug is not currently marketed here.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (multi-kinase inhibitor: VEGFR2/3, EGFR, RET) — not conventional cytotoxic chemotherapy |
| Myelosuppression Risk | Not directly reported in this evidence pack; literature-cited toxicities for this drug class center on hepatotoxicity, proteinuria, and treatment-related mortality rather than classic myelosuppression |
| Emetogenicity Classification | Low to Moderate (typical of oral small-molecule TKIs) |
| Monitoring Items | Liver function tests (per PMID 23981115), renal function/urinalysis for proteinuria (per PMID 32105149), general tolerability monitoring given class-wide treatment-related mortality signal (PMID 22651902) |
| Handling Protection | Standard oral oncology drug handling precautions recommended; not a conventional cytotoxic infusion agent |
Safety Considerations
Please refer to the package insert for safety information — official warnings, contraindications, and DDI data are marked as a Blocking data gap (DG001) in this evidence pack and could not be retrieved.
Literature-derived safety signals (from class-wide TKI studies, not vandetanib-specific label data):
- Hepatotoxicity incidence across anti-angiogenic TKIs (PMID 23981115)
- Proteinuria risk associated with VEGFR-TKIs (PMID 32105149)
- Treatment-related mortality risk across the VEGFR-TKI class (PMID 22651902)
- One literature title in the broader search directly flags vandetanib toxicity concerns in its established oncology indication (“Vandetanib: too dangerous in medullary thyroid cancer”, PMID 23185843), though this trial-related literature was surfaced for a different indication context and should be independently verified.
Conclusion and Next Steps
Decision: Hold
Rationale: The VEGFR2-driven mechanistic rationale for RCC is biologically sound and supported by one completed Phase 2 trial in VHL-associated renal tumors (n=37), but two of the four directly relevant trials terminated early with very small enrollment (n=3, n=7), and the drug’s official safety documentation (warnings, contraindications, DDI) is a Blocking data gap that prevents completion of the required S1 safety review.
To proceed, the following is needed:
- Retrieve official label/regulatory safety documentation (warnings, contraindications, DDI) — currently Blocking (DG001)
- Retrieve a formal, sourced mechanism-of-action record rather than relying on inferred rationale text (DG002)
- Clarify the reasons NCT01372813 (n=3) and NCT02495103 (n=7) were terminated early — safety-driven vs. enrollment failure
- Confirm disease-population match for NCT01191892, which was designed for urothelial rather than classic RCC
- If advancing past Hold, prioritize newer, adequately powered trials specific to clear cell or VHL-driven RCC rather than relying on trials completed a decade or more ago
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.