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/EGFR/RET) internationally approved for medullary thyroid cancer; no Danish marketing authorisation is currently on file for this drug. The TxGNN model predicts it may be effective for Renal Cell Carcinoma, with 4 clinical trials and 6 publications currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available in the Danish licensing data; literature context (PMID 24451769) indicates Vandetanib is internationally approved as a RET-kinase inhibitor for medullary thyroid cancer |
| Predicted New Indication | Renal Cell Carcinoma |
| TxGNN Prediction Score | 99.92% |
| Evidence Level | L2 (1 completed randomized Phase 2 trial) |
| Denmark Market Status | Not marketed |
| Number of Marketing Authorisations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data for Vandetanib was not returned by DrugBank in this evidence pack (data gap, High severity). Based on the literature evidence collected, Vandetanib is a multi-target tyrosine kinase inhibitor acting on VEGFR2, EGFR and RET; one review in the evidence set (PMID 26677336) explicitly groups vandetanib together with sunitinib, sorafenib and pazopanib as antiangiogenic agents targeting VEGF-driven signalling in solid tumours.
Sunitinib, sorafenib and pazopanib — drugs sharing vandetanib’s core VEGFR2-inhibition mechanism — are already established first-line treatments for renal cell carcinoma, since RCC is a highly vascularised, angiogenesis-dependent tumour. This provides a direct mechanistic rationale for the TxGNN prediction: a VEGFR2-targeting agent proven effective in one angiogenesis-driven malignancy (thyroid cancer, via RET/VEGFR inhibition) is plausible in another (renal cell carcinoma), and several early-phase trials in the evidence pack (VHL-associated renal tumors, clear cell RCC, HLRCC/SDH-associated kidney cancer) have already tested this hypothesis directly.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00566995 | Phase 2 | Completed | 37 | Tested vandetanib (ZD6474) for antiangiogenic/antitumour effect in Von Hippel-Lindau disease-associated renal tumors |
| NCT02495103 | Phase 1/2 | Terminated | 7 | Vandetanib + metformin combination in HLRCC- or SDH-associated kidney cancer and sporadic papillary RCC |
| NCT01372813 | Phase 2 | Terminated | 3 | Evaluated vandetanib for tumour shrinkage/stabilisation in advanced clear cell renal carcinoma; stopped early |
| NCT01191892 | Phase 2 (Randomized) | Completed | 82 | Randomized trial of carboplatin/gemcitabine ± vandetanib as first-line therapy in cisplatin-ineligible advanced urothelial/renal pelvis cancer |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 36302175 | 2023 | Phase II Trial | Clin Cancer Res | Guadecitabine trial in SDH-deficient tumours including HLRCC-associated renal cell carcinoma, a population resistant to conventional therapy |
| 40779213 | 2025 | Review | Clin Exp Metastasis | Discusses targeted-therapy combinations for metastatic fumarate hydratase-deficient RCC, a rare, aggressive subtype with no established regimen |
| 26677336 | 2015 | Review | OncoTargets Ther | Profiles antiangiogenic TKIs (sunitinib, sorafenib, pazopanib, vandetanib) approved across solid-tumour indications |
| 28477875 | 2017 | Review | Bull Cancer | Reviews cabozantinib MOA/efficacy in the broader context of VEGFR/RET-targeting TKIs |
| 24451769 | 2012 | Review | ASCO Educational Book | Reviews systemic therapy for advanced thyroid cancers; notes vandetanib’s FDA approval as a RET-kinase inhibitor for medullary thyroid cancer |
| 31043488 | 2019 | Preclinical | Mol Cancer Res | Mouse model of TFE3 Xp11.2-translocation RCC identifies novel therapeutic targets and a diagnostic marker (GPNMB) |
Denmark Market Information
Vandetanib currently has no marketing authorisation on file with the Danish Medicines Agency (Laegemiddelstyrelsen) — market status is Not marketed, with 0 registered authorisations.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (multi-kinase inhibitor: VEGFR2, EGFR, RET) |
| Myelosuppression Risk | Please refer to the Summary of Product Characteristics (SmPC) warnings and precautions |
| Emetogenicity Classification | Please refer to the Summary of Product Characteristics (SmPC) warnings and precautions |
| Monitoring Items | Please refer to the Summary of Product Characteristics (SmPC) warnings and precautions |
| Handling Protection | As an oral antineoplastic agent, standard institutional handling precautions for cytotoxic/targeted oncology drugs should be followed pending SmPC confirmation |
Safety Considerations
Please refer to the approved Summary of Product Characteristics (SmPC) for safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: Mechanistic rationale and early-phase clinical evidence for renal cell carcinoma are present, but a Blocking data gap exists — TFDA/SmPC warnings and contraindications are unavailable, so the candidate cannot pass initial safety screening (S1), and Vandetanib holds no marketing authorisation in Denmark.
To proceed, the following is needed:
- SmPC warnings, contraindications and drug interaction data (currently blocking)
- Confirmed mechanism of action from DrugBank
- Danish/EMA marketing authorisation status and any centralised (EMA) licence details
- Evaluation of a pathway to Danish market entry given the current “Not marketed” status
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.