*3.4.6. Axitinib*

Axitinib is an oral TKI that acts selectively inhibiting all VEGFR kinases [137]. The drug is approved by the FDA for the treatment of advanced RCC after the failure of one prior systemic therapy. In a Japanese study on 18 patients affected by various solid tumors receiving axitinib at different dosage, 16 (89%) patients experienced elevation in serum TSH above the upper limit of normal range [138].

In a phase II study on 60 patients with thyroid cancers resistant or not appropriate for 131I, who received axitinib (starting dose, 5 mg orally twice daily), no thyroid tests abnormalities were registered, except for the initial decreases in thyroglobulin seen in most patients, regardless of their clinical response to therapy. In another phase II study on 62 patients with metastatic RCC refractory to prior therapies, including sorafenib, G1-2 hypothyroidism was registered in 29% of patients [139]. In preclinical studies with axitinib inhibition of VEGFR-2 and VEGFR-3 induced by axitinib lead to thyroid capillary regression [115,140]. Again, destructive thyroiditis mediated by the destruction of thyroid capillary appears a plausible mechanism of action explaining axitinib-associated hypothyroidism.
