Chemical: Drug
vandetanib
PharmGKB contains no prescribing info for this . Contact us to report known genotype-based dosing guidelines, or if you are interested in developing guidelines.
1. Annotation of EMA Label for vandetanib and RET
Summary
The EMA European Public Assessment Report (EPAR) for vandetanib (Caprelsa) recommends testing for RET mutation status, as patients without RET mutations may have decreased benefit from vandetanib treatment.
Annotation
Vandetanib is indicated in patients with unresectable locally advanced or metastatic medullary thyroid cancer. Consideration should be given before prescribing the drug in patients with unknown or negative RET mutation status, as they may have decreased treatment benefit compared to patients with RET mutations.
Excerpts from the vandetanib (Caprelsa) EPAR:
Rearranged during transfection (RET) status
Patients without RET mutation may have a decreased benefit from vandetanib treatment and the benefit/risk balance for this group of patients may therefore differ from that of the group with RET mutations. For patients whose RET mutation status could be negative, a possible lower benefit should be taken into account before individual treatment decisions and the use of vandetanib should be carefully considered because of the treatment related risks. Therefore RET mutation testing is recommended. When establishing RET mutation status, tissue samples should be obtained if possible at the time of initiation of treatment rather than at the time of diagnosis (see sections 4.1 and 5.1).
Vandetanib also inhibits both wild type and the majority of mutated, activated forms of RET, and significantly inhibits the proliferation of MTC cell lines in vitro.
For the complete drug label text with sections containing pharmacogenetic information highlighted, see the vandetanib (Caprelsa) EMA drug label.
*Disclaimer: The contents of this page have not been endorsed by the EMA and are the sole responsibility of PharmGKB.
Genes and/or phenotypes found in this label
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Thyroid Neoplasms
- efficacy, Indications & usage section, Information for patients section
- source: European Medicines Agency
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CYP3A4
- metabolism/PK, Drug interactions section, Pharmacokinetics section, Warnings and precautions section
- source: European Medicines Agency
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KDR
- efficacy, Pharmacodynamics section
- source: European Medicines Agency
-
RET
- efficacy, Indications & usage section, Clinical studies section, Pharmacodynamics section, Warnings and precautions section
- source: European Medicines Agency
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SLC22A2
- metabolism/PK, Drug interactions section
- source: European Medicines Agency
PharmGKB contains no Clinical Variants that meet the highest level of criteria.
Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.
The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.
Overview
- CAPRELSA
- ZACTIMA
- ZD6474
PharmGKB Accession Id
PA166118341
Type(s):
Drug
Description
Vandetanib is a novel multitargeted kinase inhibitor exhibiting potent activity against vascular endothelial growth factor receptor-2 (coded for by KDR) and with lower activity against VEGFR-3 (FLT4, EGFR and RET [Article:17136225] [Article:17243944].
Source: PharmGKB [Article:17243944] [Article:17136225]
Indication
Vandetanib is FDA approved for unresectable, locally advanced, or metastatic medullary thyroid cancer.
Source: PharmGKB
Other Vocabularies
- ATC: Protein kinase inhibitors (L01XE)
- RxNorm: Vandetanib (1098413)
Information pulled from DrugBank has not been reviewed by PharmGKB.
Chemical Properties
SMILES
CN1CCC(CC1)COC2=C(C=C3C(=C2)N=CN=C3NC4=C(C=C(C=C4)Br)F)OC
Source: PubChem
InChI String
InChI=1S/C22H24BrFN4O2/c1-28-7-5-14(6-8-28)12-30-21-11-19-16(10-20(21)29-2)22(26-13-25-19)27-18-4-3-15(23)9-17(18)24/h3-4,9-11,13-14H,5-8,12H2,1-2H3,(H,25,26,27)
Source: PubChem
PharmGKB Curated Pathways
Pathways created internally by PharmGKB based primarily on literature evidence.
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VEGF Signaling Pathway
Model endothelial cell displaying genes of the VEGF signalling pathway and the sites at which bevacizumab, sorafenib, sunitinib, brivanib and cilengitide are known to act.
Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.
Curated Information ?
Drug Targets
| Gene | Description |
|---|---|
| EGFR | [PMID: 17136225] (source: PharmGKB ) |
| KDR | [PMID: 17136225] (source: PharmGKB ) |
| RET | [PMID: 17136225] (source: PharmGKB ) |
Curated Information ?
| Evidence | Disease |
|---|---|
|
Carcinoma, Non-Small-Cell Lung |
| Thyroid Neoplasms |
Publications related to vandetanib: 6
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Meta-analysis of the risks of hypertension and QTc prolongation in patients with advanced non-small cell lung cancer who were receiving vandetanib. European journal of clinical pharmacology. 2015. Liu Ying, et al.
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The genetics of pro-arrhythmic adverse drug reactions. British journal of clinical pharmacology. 2014. Petropoulou Evmorfia, et al.
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EMA Initiatives and Perspectives on Pharmacogenomics. British journal of clinical pharmacology. 2014. Ehmann Falk, et al.
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Role of OATP-1B1 and/or OATP-1B3 in hepatic disposition of tyrosine kinase inhibitors. Drug metabolism and drug interactions. 2014. Khurana Varun, et al.
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Vandetanib (ZD6474): an orally available receptor tyrosine kinase inhibitor that selectively targets pathways critical for tumor growth and angiogenesis. Expert opinion on investigational drugs. 2007. Herbst Roy S, et al.
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Vandetanib, a novel multitargeted kinase inhibitor, in cancer therapy. Drugs of today (Barcelona, Spain : 1998). 2006. Sathornsumetee Sith, et al.
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LinkOuts
- PubChem Compound:
- Vandetanib (3081361)
Clinical Trials
These are trials that mention vandetanib and are related to either pharmacogenetics or pharmacogenomics.
NURSA Datasets
No NURSA datasets available.