Thyroid function test abnormalities in patients with metastatic renal cell carcinoma treated with sorafenib

Abstract

Background: Sorafenib is an orally bioavailable vascular endothelial growth factor receptor (VEGFR) inhibitor with antitumor activity in metastatic renal cell carcinoma (RCC). Sunitinib, also a VEGFR inhibitor, induces biochemical hypothyroidism in 85% of metastatic RCC patients, the majority of whom have signs or symptoms of hypothyroidism. Hence, the incidence of thyroid function test (TFT) abnormalities in patients with metastatic RCC receiving sorafenib was investigated.Patients and methods: Sixty-eight patients with metastatic RCC were treated with sorafenib at the Cleveland Clinic Taussig Cancer Center, and 39 patients had TFTs available.Results: Eight patients (21%) had thyroid dysfunction possibly caused by sorafenib [seven hypothyroidism (18%) and one hyperthyroidism (3%)] and eight additional patients (21%) had findings compatible with nonthyroidal illness. Only two patients had clinical signs and symptoms secondary to thyroid dysfunction and received thyroid hormone replacement.Conclusions: In summary, clinically significant TFT abnormalities were not common in patients treated with sorafenib, and replacement therapy was rarely indicated. TFTs should be measured before sorafenib therapy in RCC patients and subsequently only if clinically indicated.

The clinical implications of sunitinib-induced hypothyroidism: a prospective evaluation

“…Indirectly, sunitinib may affect the thyroid by interfering with the metabolism of T4/T3 hormones, or with thyroid hormone action at the pituitary level. In patients treated with sorafenib, another tyrosine kinase inhibitor, thyroid dysfunction seems not to be a frequent side effect (Tamaskar et al, 2008;Wolter et al, manuscript in preparation).…”

Hypothyroidism related to tyrosine kinase inhibitors: an emerging toxic effect of targeted therapy

“…tamaskar et al 33 retrospectively investi gated the incidence of tFt abnormalities in 39 patients with metastatic rCC treated with 400 mg sorafenib twice daily. most patients had received at least one prior treat ment.…”

“…six of these patients had mild tsH level elevations (5.5-10.0 mu/l). another patient showed a rapid onset of hypothyroidism with tsH level rising from 5.74 to 160.64 mu/l, and t3 level 33 No specific data Cellular abnormalities in thyroid-targeted transgenic mice 61 Progressive damage to thyroid function…”

“…However, only a pro portion of patients who developed hypothyroidism while receiving sunitinib and lt4 rx (50-79%) had resolution of symptoms related to hypothyroidism. 33 the therapeutic relevance of early diagnosis of hypo thyroidism or even subclinical hypothyroidism is as yet unknown. Definitive data on the advantage of early treat ment of subclinical hypothyroidism are not available from prospective studies.…”

“…29,32 sorafenib has been reported to cause hypothyroidism in 18% of patients with metastatic rCC in only one study. 33 several possible mechanisms that lead to sustained tKi related thyroid toxic effects have been suggested, but pharmacological and preclinical data are lacking. understanding whether sunitinib related or sorafenib related hypothyroidism is dependent on the drug's direct mechanism of action (i.e.…”