Thyroid profile during the alternative Sunitinib dosing 2/1 schedule in metastatic renal cell carcinoma
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Hypothyroidism is a common side effect of Sunitinib (SUN) treatment in metastatic renal cell carcinoma (mRCC) patients. We aimed to evaluate thyroid profile during the alternative 2/1 SUN treatment schedule and to assess the predictive value of hypothyroidism in terms of survival.
We performed a prospective observational study enrolling 42 consecutive mRCC patients starting first-line alternative SUN dosing 2/1 schedule. Thyroid function was assessed at baseline and during the first three SUN cycles (1 cycle = 6 weeks = 2 ON/1 OFF + 2 ON/1 OFF), and then after 6 and 12 months. Thyroid ultrasound was performed at baseline and after 3, 6, and 12 months.
Subclinical hypothyroidism developed in 24% of patients during the first cycle; in other 24% in the second cycle and in 14% in the third cycle. The highest TSH values were reached during the second cycle, ON phase (6.58 ± 5.74 μI U/l). We observed a reduction in thyroid size, in echogenicity and in parenchymal perfusion in all patients. Progression-free survival (PFS) tended to be longer in patients with TSH ≥ 5 μI U/ml during the second cycle (p = 0.069). TSH level was an independent risk factor for PFS in men (p = 0.009) but not in women (p = 0.285).
This is the first study investigating functional and morphological effects on thyroid during the alternative 2/1 SUN schedule in mRCC patients. We detected an early onset of subclinical hypothyroidism, observing the association between TSH ≥ 5 μI U/ml and: (i) longer PFS in men; (ii) progressive decrease of thyroid size in absence of significant changes in autoimmune thyroid profile.
KeywordsTyrosine kinase inhibitors Hypothyroidism TSH Target therapy
renal cell carcinoma
metastatic renal cell carcinoma
von Hippel Lindau
vascular endothelial growth factor
platelet-derived growth factor
vascular endothelial growth factor receptor
platelet-derived growth factor receptor
tyrosine kinase inhibitors
progression free survival
overall response rate
free survival rate
time to progression
common toxicity criteria
thyroid stimulating hormone
anti-thyroid peroxidase antibody
follicle stimulating hormone
type III deiodinase
response evaluation criteria in solid tumors
ordinary least squares
L.R., C.P., E.S., and E.G. designed and coordinated the study. F.L. and G.D.B. enrolled and followed patients. L.R., E.S., D.G., R.L., and M.T. followed and managed endocrine aspects of patients and performed US images. C.P., E.G., and A.F. performed quality control checks and separately analyzed thyroid US images. C.P. performed statistical analysis of the data. A.L. verified the analytic method. L.R., E.S., E.G., C.P., and A.F. contributed to the final version of the manuscript.
Compliance with ethical standards
Conflict of interest
All authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the iwenstitutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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