 | |
| Clinical data | |
|---|---|
| Trade names | Lenvima, others |
| Other names | E7080 |
| AHFS/Drugs.com | Monograph |
| License data | |
| Pregnancy category |
|
| Routes of administration | By mouth |
| ATC code | |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Bioavailability | 85% (estimated) |
| Protein binding | 98–99% |
| Metabolism | CYP3A4,aldehyde oxidase, non-enzymatic |
| Metabolites | Desmethyl-lenvatinib (M2) and others |
| Eliminationhalf-life | 28 hours |
| Excretion | ~65%feces, 25%urine |
| Identifiers | |
| |
| CAS Number | |
| PubChemCID | |
| IUPHAR/BPS | |
| DrugBank |
|
| ChemSpider |
|
| UNII | |
| KEGG | |
| ChEBI | |
| ChEMBL | |
| CompTox Dashboard(EPA) | |
| Chemical and physical data | |
| Formula | C21H19ClN4O4 |
| Molar mass | 426.86 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
 N Y (what is this?) (verify) | |
Lenvatinib, sold under the brand nameLenvima among others, is ananti-cancer medication for the treatment of certain kinds ofthyroid cancer and for other cancers as well. It was developed byEisai Co. and acts as a multiplekinase inhibitor against theVEGFR1,VEGFR2 andVEGFR3 kinases.[4]
Lenvatinib is approved (since 2015) for the treatment of differentiatedthyroid cancer that is either locally recurrent ormetastatic, progressive, and did not respond to treatment withradioactive iodine (radioiodine).[5][6]
In May 2016, the USFood and Drug Administration (FDA) approved it (in combination witheverolimus) for the treatment of advancedrenal cell carcinoma following one prior anti-angiogenic therapy.[7]
The drug is also approved in the US and in the European Union forhepatocellular carcinoma that cannot be removed surgically in patients who have not received cancer therapy by mouth or injection.[8][9]
Hypertension (high blood pressure) was the most common side effect in studies (73% of patients, versus 16% in theplacebo group), followed by diarrhoea (67% vs. 17%) andfatigue (67% vs. 35%).[6] Other common side effects included decreased appetite,hypotension (low blood pressure),thrombocytopenia (low blood platelet count), nausea, muscle and bone pain.[5]
As lenvatinib moderatelyprolongs QT time, addition of other drugs with this property could increase the risk of a type of abnormal heart rhythm, namelytorsades de pointes. No relevant interactions withenzyme inhibitors andinducers are expected.[6]
Lenvatinib is a multi-targetedreceptor tyrosine kinase inhibitor that blocks several key proteins involved in cancer-relatedsignalling pathways. It inhibits the three mainvascular endothelial growth factor receptors (VEGFR1, VEGFR2, and VEGFR3), as well asfibroblast growth factor receptors (FGFR1, FGFR2, FGFR3, and FGFR4),platelet-derived growth factor receptor (PDGFR) alpha,c-Kit, and theRET proto-oncogene. Inhibition of VEGFR2 is considered the primary cause of the most common side effect, hypertension.[5] Lenvatinib exhibits strong inhibitory activity againstVEGFR1, 2, and 3 RTKs, withKi values of 1.3, 0.74, and 0.71 nM, respectively. It also inhibitsFGFR1, 2, and 3 RTKs (Ki = 22, 8.2, and 15 nM, respectively), as well asRET andKIT (Ki = 1.5 and 11 nM, respectively).[10]
Lenvatinib is absorbed quickly from the gut, reaching peakblood plasma concentrations after one to four hours (three to seven hours if taken with food).Bioavailability is estimated to be about 85%. The substance is almost completely (98–99%) bound toplasma proteins, mainlyalbumin.[5]
Lenvatinib is metabolized by the liver enzymeCYP3A4 to desmethyl-lenvatinib (M2). M2 and lenvatinib itself are oxidized byaldehyde oxidase (AO) to substances called M2' and M3',[11] the main metabolites in the feces. Another metabolite, also mediated by a CYP enzyme, is theN-oxide M3. Non-enzymatic metabolization also occurs, resulting in a low potential for interactions with enzyme inhibitors and inducers.[5]
Terminal half-life is 28 hours, with about two thirds being excreted via the feces, and one quarter via the urine.[5]
Lenvatinib is used in form of themesylate salt (CAS number857890-39-2 ).
Aphase I clinical trial in cancer patients was performed in 2006.[12] A phase III trial treating thyroid cancer patients started in March 2011.[13]
Lenvatinib was grantedorphan drug status for treatment of various types of thyroid cancer that do not respond to radioiodine in the US and Japan in 2012 and in Europe in 2013.[14]
In February 2015, theU.S. FDA approved lenvatinib for treatment of progressive, radioiodine refractory differentiated thyroid cancer.[15] In May 2015,European Medicines Agency (EMA) approved the drug for the same indication.[16]
In May 2016, the FDA approved it (in combination witheverolimus) for the treatment of advancedrenal cell carcinoma following one prior anti-angiogenic therapy.[7]
In August 2018, the FDA approved lenvatinib for the first-line treatment of people with unresectable hepatocellular carcinoma (HCC).[9]
