title: Lenvatinib: a new option for the treatment of advanced iodine refractory differentiated thyroid cancer?
abstract: Lenvatinib mesylate (E7080; 4-[3-chloro-4-(N'-cyclopropylureido) phenoxy] 7-methoxyquinoline-6-carboxamide mesylate) is an oral molecule that inhibits multiple tyrosine kinase receptors such as VEGF-R-1-3, FGF-R-1-4, RET, c-KIT and PDGF-R-β. Phase I studies identified the maximum tolerated dose to be 25 mg daily that, in fasting treated patients, is rapidly absorbed with maximum concentrations achieved within 3 h of administration. In these studies, lenvatinib showed activity in solid tumors. Subsequently, Phase II studies in thyroid cancer, in particular differentiated thyroid cancer (DTC), confirmed good clinically significant activity and the recently published Phase III SELECT trial reported median progression-free survival was 18.3 months with lenvatinib versus 3.6 months with placebo (hazard ratio for progression or death: 0.21; 99% CI: 0.14-0.31; p < 0.001). Treatment-related adverse effects occurred in more than 40% of patients on lenvatinib. These were hypertension (in 67.8% of the patients), diarrhea (in 59.4%), fatigue or asthenia (in 59.0%), decreased appetite (in 50.2%), decreased weight (in 46.4%) and nausea (in 41.0%). Discontinuations of lenvatinib because of adverse effects occurred in 37 patients (14.2%) compared with three patients who received placebo (2.3%). Six of 20 deaths in patients on lenvatinib were considered to be drug-related. Lenvatinib has been licensed by the US FDA and EMA based on these data and provides an option for the treatment of radioiodine refractory DTC.
authors.affiliation: The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, SM2 5PT, UK.
authors.forename: Loredana
authors.initials: L
authors.lastname: Lorusso
authors.affiliation: The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, SM2 5PT, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Newbold
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D007457:Iodine Radioisotopes / Q000494:pharmacology*; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D011804:Quinolines / Q000627:therapeutic use*; D011836:Radiation Tolerance; D019275:Radiopharmaceuticals / Q000494:pharmacology*; D015398:Signal Transduction; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007457:Iodine Radioisotopes; D010671:Phenylurea Compounds; D011804:Quinolines; D019275:Radiopharmaceuticals; C531958:lenvatinib
keywords: E7080; lenvatinib; thyroid cancer; tyrosine kinase inhibitor treatment