Thyroid profile during the alternative Sunitinib dosing 2/1 schedule in metastatic renal cell carcinoma

• Published in: Endocrine Vol. 67; no. 3; pp. 597 - 604
• Main Authors: Rizza, L., Sbardella, E., Gianfrilli, D., Lauretta, R., Tenuta, M., Del Bene, G., Longo, F., Faggiano, A., Lenzi, A., Giannetta, E., Pozza, C.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.03.2020; Springer Nature B.V
• Subjects: Diabetes; Endocrinology; Humanities and Social Sciences; Hypothyroidism; Internal Medicine; Kidney cancer; Medicine; Medicine & Public Health; Metastases; Metastasis; multidisciplinary; Original Article; Perfusion; Renal cell carcinoma; Risk factors; Science; Thyroid; Thyroid gland; Thyroid-stimulating hormone; Ultrasound; TSH; Hypothyroidism; Target therapy; Tyrosine kinase inhibitors
• ISSN: 1355-008X; 1559-0100
• DOI: 10.1007/s12020-019-02088-4

Purpose 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. Methods 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. Results 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). Conclusions 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.