Title:Lenvatinib in the Therapy of Aggressive Thyroid Cancer: State of the Art and New Perspectives with Patents Recently Applied
Volume: 13
Issue: 2
Author(s): Silvia M. Ferrari, Ilaria Ruffilli, Marco Centanni, Camilla Virili, Gabriele Materazzi, Magdalini Alexopoulou, Mario Miccoli, Alessandro Antonelli*Poupak Fallahi
Affiliation:
- Department of Clinical and Experimental Medicine, University of Pisa, Via Savi, 10, I-56126, Pisa,Italy
Keywords:
Anaplastic thyroid cancer, dedifferentiated thyroid cancer, follicular thyroid cancer, lenvatinib, papillary thyroid
cancer, tyrosine kinase inhibitors.
Abstract: Background and Objective: Lenvatinib is an oral, multitargeted Tyrosine Kinase Inhibitor
(TKI) of Vascular Endothelial Growth Factor Receptors (VEGFR1-VEGFR3), fibroblast growth factor
receptors (FGFR1-FGFR4), Platelet-Derived Growth Factor Receptor (PDGFR)α, rearranged during
transfection (RET), and v-kit (KIT) signaling networks implicated in tumor angiogenesis.
Method: Here, we review the scientific literature about lenvatinib in the treatment of thyroid cancer.
Results: In vitro studies have shown antineoplastic activity of lenvatinib in Differentiated Thyroid Cancer
(DTC), mainly because of its antiangiogenetic effects, but a slight effect on thyroid cancer cell proliferation
has been shown.
In vivo Phase II, and Phase III studies in patients with aggressive DTC not responsive to radioiodine,
have shown that lenvatinib administration was associated with an amelioration in Progression-Free Survival
(PFS) with respect to placebo (median PFS 18.2 vs. 3.6 months). However, overall survival was
not significantly changed. Lenvatinib is also effective in patients resistant to sorafenib as salvage therapy.
Adverse effects of any grade occur in more than 40% of lenvatinib-treated patients, mainly hypertension,
diarrhea, asthenia or fatigue, nausea, decreased appetite, and decreased weight. Discontinuations of
the therapy because of adverse effects occur in about 14% of patients. Moreover, deaths considered to
be drug-related can occur.
Conclusion: On the basis of the above-mentioned considerations, it is necessary to prove the effectiveness
of lenvatinib in the context of associated moderate to severe toxicities requiring frequent dose reduction
and delays, and for this reason, many interesting patents have been recently applied.
