Vandetanib

證據等級: L5

預測適應症: 10 個

Vandetanib: From Medullary Thyroid Cancer to Renal Cell Carcinoma

One-Sentence Summary

Vandetanib is a multi-target tyrosine kinase inhibitor (VEGFR2/EGFR/RET) internationally approved for advanced medullary thyroid cancer (MTC), though it is not currently marketed in Norway. The TxGNN model predicts it may also be effective for Renal Cell Carcinoma, with 4 clinical trials (2 completed, 2 terminated) and 6 publications currently supporting this direction — though the trial evidence is limited by small sample sizes and early termination.

Quick Overview

Item	Content
Original Indication	Not marketed in Norway (0 authorizations); internationally approved for Medullary Thyroid Cancer (MTC), per literature evidence (PMID 24451769, 32691271)
Predicted New Indication	Renal Cell Carcinoma (disease)
TxGNN Prediction Score	99.92%
Evidence Level	L3 (Research Question / Decision Stage S1)
Norway Market Status	✗ Not Marketed (未上市)
Number of Authorizations	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Formal mechanism-of-action documentation for vandetanib is currently a data gap (DG002, High severity). Based on the information available within this evidence pack, vandetanib is characterized as a VEGFR2/EGFR/RET multi-target tyrosine kinase inhibitor — the same antiangiogenic mechanism shared by already-approved RCC drugs such as sunitinib, pazopanib, and cabozantinib (see literature PMID 28477875, 26677336).

Renal cell carcinoma, particularly clear cell and VHL-associated subtypes, is strongly driven by VEGF/HIF pathway overactivation, making VEGFR2 inhibition mechanistically plausible. This is partly supported by a completed Phase 2 trial in VHL-associated renal tumors (NCT00566995, n=37, grade B relevance). However, vandetanib's direct clinical evidence in RCC remains sparse compared to its established, RET-driven mechanism in MTC — most RCC-specific trials for vandetanib were terminated early or severely underpowered (n=3–7), suggesting the mechanistic rationale has not yet translated into robust clinical proof for this specific drug (as opposed to its drug class).

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00566995	Phase 2	Completed	37	Vandetanib in VHL-associated renal tumors; single-arm, mechanism-relevant population; no reported efficacy outcome data in this pack (grade B)
NCT02495103	Phase 1/2	Terminated	7	Vandetanib + metformin in HLRCC/SDH-associated or sporadic papillary RCC; extremely small sample, rare subtype (grade C)
NCT01372813	Phase 2	Terminated	3	Vandetanib monotherapy in advanced clear cell RCC; terminated with n=3, no statistical power (grade C)
NCT01191892	Phase 2	Completed	82	Carboplatin/gemcitabine ± vandetanib; regimen is atypical for RCC (more consistent with NSCLC/urothelial protocols) — indication tagging flagged as needing manual verification (grade C)

Literature Evidence

PMID	Year	Type	Journal	Key Findings
40779213	2025	Review	Clin Exp Metastasis	Targeted/epigenetic strategies in fumarate hydratase-deficient RCC; no direct vandetanib efficacy data
36302175	2023	Phase 2 (other drug)	Clin Cancer Res	Guadecitabine trial in SDH-deficient tumors including HLRCC-RCC; comparator mechanism context only
31043488	2019	Preclinical (mouse model)	Mol Cancer Res	TFE3-RCC mouse model identifies novel therapeutic targets; no vandetanib-specific data
26677336	2015	Review (other drug)	OncoTargets Ther	Antiangiogenic TKI class review (sunitinib, sorafenib, pazopanib, vandetanib) across solid tumors
28477875	2017	Review (other drug)	Bull Cancer	Cabozantinib MOA/efficacy review; contextualizes shared VEGFR2/RET target class
24451769	2012	Review	ASCO Educational Book	Confirms vandetanib's FDA-approved RET-driven mechanism in medullary thyroid cancer — supports original indication context

Other Predicted Indications (Ranks 2–10, Lower Evidence)

These additional TxGNN-predicted candidates share high prediction scores but lack direct clinical or literature support; all are at decision stage S0 (Hold) except the two entries below.

Rank	Disease	TxGNN Score	Evidence Level	Recommendation	Note
2	RCC (Xp11.2/TFE3 fusion)	99.90%	L5	Hold	No trials/literature; network-similarity inference only
3	RCC associated with neuroblastoma	99.90%	L5	Hold	No direct evidence; rare disease association
4	Unclassified RCC	99.90%	L5	Hold	No direct evidence
5	Renal pelvis carcinoma	99.88%	L4	Hold	Sole trial (NCT01191892) has questionable indication tagging; histology differs from RCC
6	Clear cell renal carcinoma	99.87%	L3	Research Question	Strongest sub-evidence: VHL-population trial (NCT00566995) + 16 literature items; overlaps with rank-1 rationale
7	Childhood kidney cell carcinoma	99.86%	L5	Hold	No pediatric trials/literature; safety in children unestablished
8	Renal carcinoma (general)	99.83%	L3	Research Question	Aggregates same trials/literature as ranks 1 and 6
9	Angiolipoma	99.82%	L5	Hold	No known VEGFR/EGFR/RET pathology link; likely network artifact (e.g., tuberous sclerosis co-morbidity)
10	Familial spontaneous pneumothorax	99.76%	L5	Hold	No plausible mechanistic link; likely prediction artifact (e.g., Birt-Hogg-Dubé network proximity); not recommended for further investment

Norway Market Information

Vandetanib currently holds 0 marketing authorizations in Norway (market status: 未上市 / Not Marketed). No product listings, dosage forms, or approved indication text are available in the regulatory dataset for this drug.

Cytotoxicity

Vandetanib is an antineoplastic agent (targeted kinase inhibitor class; approved indication involves cancer treatment), so this section applies.

Item	Content
Cytotoxicity Classification	Targeted therapy — multi-target tyrosine kinase inhibitor (VEGFR2, EGFR, RET)
Myelosuppression Risk	Low — TKIs generally cause less myelosuppression than conventional cytotoxics; class-wide hepatotoxicity (PMID 23981115) and proteinuria (PMID 32105149) are more prominent reported risks
Emetogenicity Classification	Low to Moderate (typical for oral TKIs)
Monitoring Items	Liver function tests, renal function/urinalysis (proteinuria monitoring), blood pressure, baseline CBC; a class-wide treatment-related mortality meta-analysis (PMID 22651902) supports close monitoring during therapy
Handling Protection	TFDA package insert is not yet available (Blocking data gap, DG001) — formal handling protocol cannot be confirmed; standard oral antineoplastic handling precautions recommended pending resolution

Safety Considerations

Please refer to the package insert for safety information. Formal warnings, contraindications, and drug-drug interaction data for vandetanib are not yet available in this evidence pack (DG001, Blocking severity) — this gap currently prevents completion of the S1 safety pre-assessment.

Conclusion and Next Steps

Decision: Hold

Rationale: The strongest candidate indication (renal cell carcinoma, rank 1) reaches only evidence level L3 (Research Question stage), supported by trials that are largely terminated or severely underpowered (n=3–7), with only one adequately sized completed trial (n=37) in a rare VHL-associated subgroup. Critically, TFDA safety/warning data is a Blocking data gap, which prevents the mandatory S1 safety pre-assessment from being completed, and the drug is not currently marketed in Norway.

To proceed, the following is needed:

Resolve DG001 (Blocking): obtain TFDA or equivalent regulatory package insert data on warnings and contraindications
Resolve DG002 (High): obtain formal MOA documentation from DrugBank or equivalent source
Clarify apparent indication mislabeling in NCT01191892 (regimen more consistent with NSCLC/urothelial than RCC)
Identify larger, adequately powered RCC-specific trials for vandetanib (current trials are terminated or underpowered)
Assess Norway market entry / import pathway feasibility given 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.