L Rizza1, E Sbardella2, D Gianfrilli2, R Lauretta3, M Tenuta2, G Del Bene4, F Longo4, A Faggiano2, A Lenzi2, E Giannetta2, C Pozza5. 1. Endocrinology Unit, Department of Oncology and Medical Specialities, AO San Camillo-Forlanini, Rome, Italy. 2. Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy. 3. Internal Medicine, Angiolini Hospital of Bagno di Romagna, Forlì Cesena, Italy. 4. Department of Radiological, Oncological and Anatomopathological Sciences, Sapienza University of Rome, Rome, Italy. 5. Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy. carlotta.pozza@uniroma1.it.
Abstract
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.
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 mRCCpatients 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 mRCCpatients. 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.
Authors: Giuseppe Di Lorenzo; Camillo Porta; Joaquim Bellmunt; Cora Sternberg; Ziya Kirkali; Michael Staehler; Steven Joniau; Francesco Montorsi; Carlo Buonerba Journal: Eur Urol Date: 2011-01-14 Impact factor: 20.096
Authors: Eric Raymond; Laetitia Dahan; Jean-Luc Raoul; Yung-Jue Bang; Ivan Borbath; Catherine Lombard-Bohas; Juan Valle; Peter Metrakos; Denis Smith; Aaron Vinik; Jen-Shi Chen; Dieter Hörsch; Pascal Hammel; Bertram Wiedenmann; Eric Van Cutsem; Shem Patyna; Dongrui Ray Lu; Carolyn Blanckmeister; Richard Chao; Philippe Ruszniewski Journal: N Engl J Med Date: 2011-02-10 Impact factor: 91.245
Authors: Dirk B Mendel; A Douglas Laird; Xiaohua Xin; Sharianne G Louie; James G Christensen; Guangmin Li; Randall E Schreck; Tinya J Abrams; Theresa J Ngai; Leslie B Lee; Lesley J Murray; Jeremy Carver; Emily Chan; Katherine G Moss; Joshua O Haznedar; Juthamas Sukbuntherng; Robert A Blake; Li Sun; Cho Tang; Todd Miller; Sheri Shirazian; Gerald McMahon; Julie M Cherrington Journal: Clin Cancer Res Date: 2003-01 Impact factor: 12.531
Authors: Brett E Houk; Carlo L Bello; Bill Poland; Lee S Rosen; George D Demetri; Robert J Motzer Journal: Cancer Chemother Pharmacol Date: 2009-12-05 Impact factor: 3.333
Authors: Robert J Motzer; Thomas E Hutson; David Cella; James Reeves; Robert Hawkins; Jun Guo; Paul Nathan; Michael Staehler; Paul de Souza; Jaime R Merchan; Ekaterini Boleti; Kate Fife; Jie Jin; Robert Jones; Hirotsugu Uemura; Ugo De Giorgi; Ulrika Harmenberg; Jinwan Wang; Cora N Sternberg; Keith Deen; Lauren McCann; Michelle D Hackshaw; Rocco Crescenzo; Lini N Pandite; Toni K Choueiri Journal: N Engl J Med Date: 2013-08-22 Impact factor: 91.245
Authors: Robert J Motzer; Thomas E Hutson; Piotr Tomczak; M Dror Michaelson; Ronald M Bukowski; Stéphane Oudard; Sylvie Negrier; Cezary Szczylik; Roberto Pili; Georg A Bjarnason; Xavier Garcia-del-Muro; Jeffrey A Sosman; Ewa Solska; George Wilding; John A Thompson; Sindy T Kim; Isan Chen; Xin Huang; Robert A Figlin Journal: J Clin Oncol Date: 2009-06-01 Impact factor: 44.544
Authors: J L Lee; M K Kim; I Park; J-H Ahn; D H Lee; H M Ryoo; C Song; B Hong; J H Hong; H Ahn Journal: Ann Oncol Date: 2015-09-07 Impact factor: 32.976
Authors: M E Gore; C Szczylik; C Porta; S Bracarda; G A Bjarnason; S Oudard; S-H Lee; J Haanen; D Castellano; E Vrdoljak; P Schöffski; P Mainwaring; R E Hawkins; L Crinò; T M Kim; G Carteni; W E E Eberhardt; K Zhang; K Fly; E Matczak; M J Lechuga; S Hariharan; R Bukowski Journal: Br J Cancer Date: 2015-06-18 Impact factor: 7.640
Authors: T Anders Olsen; Tony Zibo Zhuang; Sarah Caulfield; Dylan J Martini; Jacqueline T Brown; Bradley C Carthon; Omer Kucuk; Wayne Harris; Mehmet Asim Bilen; Bassel Nazha Journal: Front Endocrinol (Lausanne) Date: 2022-03-22 Impact factor: 5.555