Lenvatinib is an anti-cancer drug for the treatment of certain kinds of thyroid cancer and for other cancers as well. It was developed by Eisai Co. and acts as a multiple kinase inhibitor against the VEGFR1, VEGFR2 and VEGFR3 kinases.
Medical uses
Lenvatinib is approved for the treatment of differentiated thyroid cancer that is either locally recurrent or metastatic, progressive, and did not respond to treatment with radioactive iodine. In May 2016, the US FDA approved it for the treatment of advanced renal cell carcinoma following one prior anti-angiogenic therapy. The drug is also approved in the US and in Europe for hepatocellular carcinoma that cannot be removed surgically in patients who have not received cancer therapy by mouth or injection.
Adverse effects
was the most common side effect in studies, followed by diarrhoea and fatigue. Other common side effects included decreased appetite, hypotension, thrombocytopenia, nausea, muscle and bone pain.
Interactions
As lenvatinib moderately prolongs QT time, addition of other drugs with this property could increase the risk of a type of abnormal heart rhythm, namely torsades de pointes. No relevant interactions with enzyme inhibitors and inducers are expected.
Lenvatinib is absorbed quickly from the gut, reaching peak blood plasma concentrations after one to four hours. Bioavailability is estimated to be about 85%. The substance is almost completely bound to plasma proteins, mainly albumin. enzymes, and further metabolized to the quinolinones M2' and M3' by aldehyde oxidase. Lenvatinib is metabolized by the liver enzymeCYP3A4 to desmethyl-lenvatinib. M2 and lenvatinib itself are oxidized by aldehyde oxidase to substances called M2' and M3', the main metabolites in the feces. Another metabolite, also mediated by a CYP enzyme, is the N-oxide M3. Non-enzymatic metabolization also occurs, resulting in a low potential for interactions with enzyme inhibitors and inducers. Terminal half-life is 28 hours, with about two thirds being excreted via the feces, and one quarter via the urine.
A phase I clinical trial in cancer patients was performed in 2006. A phase III trial treating thyroid cancer patients started in March 2011. Lenvatinib was granted orphan 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. In February 2015, the U.S. FDA approved lenvatinib for treatment of progressive, radioiodine refractory differentiated thyroid cancer. In May 2015, European Medicines Agency approved the drug for the same indication. In May 2016, the FDA approved it for the treatment of advanced renal cell carcinoma following one prior anti-angiogenic therapy. In August 2018, the FDA lenvatinib for first-line treatment of patients with unresectable hepatocellular carcinoma.
