Alteration of thyroid functions in patients with renal cell carcinoma treated with tyrosine kinase inhibitors; Turkish population study.

Yıl 2016, Cilt: 2 Sayı: 4, 144 - 148, 30.12.2016

Cemil Bilir İbrahim Yıldız Ahmet Bilici Mahmut Uçar Veli Berk Yaşar Yıldız Ozan Yazıcı Gökşen İnanç İmamoğlu Nuri Karadurmuş Kezban Nur Pilancı Erkan Arpacı Özgür Tanrıverdi Ebru Karcı Süleyman Temiz Erdinç Nayır Esin Oktay Pınar Dal İbrahim Petekkaya Onur Yağmurkaya Ceyhun Varım

Öz

Background Studies investigated different side effects of TKIs such as hypertension, dermatologic side effects and hormonal changes. Thyroid hormones

change is take an interest for last decade and phase 2 and 3 trial result had been analyzed retrospectively for this reason.

Method A totally 246 metastatic renal cell carcinoma patients who were treated with TKI included in the study and they recruited from over 10 different oncology clinics.

Results In the study 246 mRCC patients included and mean age was 60 (±8), and 183 (74%) of them were male, 63 (24%) of them were female.Following TKI therapy 15 patients (6%) became as a hyperthyroidic, 83 patients (34%) became hypothyroidic and remaining 148 patients

had in normal range for TSH levels. When we subgroup the patients according to the TSH change, in 38 patients (15.4%) had THS decreasing at least 50% from baseline and 128 patients (52%) has elevated THS levels as described previous range. In survival analyses, became hyperthyroidic patients had significantly longer OS than became hypothyrodic patients (25.4 vs 14 months, P=0.036) but no significantly differ than remained normothyroidic patients (25.4 vs 18 months, P=0.16).

Conclusion patients who had decreasing TSH levels under the treatment of TKI should have significantly higher overall survival but, hypothyroid patientsdon’t.

Anahtar Kelimeler

THS, tyrosine kinase inhibitor, survival, predictive

Kaynakça

• Mathew A, Devesa SS, Fraumeni JF Jr & Chow WH. Global increases in kidney cancer incidence, 1973–1992. European Journal of CancerPrevention 2002; 11; 171–178.
• Aydın S. Türkiye’de üriner sistem kanserlerin görülme sikliği. Türk Üroloji Dergisi. 2007; 33: 392-397.
• Rabinovitch RA, Zelefsky MJ, Gaynor JJ & Fuks Z. Patterns of failure following surgical resection of renal cell carcinoma: implications for adjuvant local and systemic therapy. Journal of Clinical Oncology 1997; 12: 206–212.
• Bianchi L, Rossi L, Tomao F, Papa A, Zoratto F, Tomao S. Thyroid dysfunction and tyrosine kinase inhibitors in renal cell carcinoma. Endocrine-Related Cancer 2013; 20: 233–245.
• Motzer RJ, Michaelson MD, Redman BG, et al. Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet derived growth factor receptor, in patients with metastatic renal cell carcinoma. Journal of Clinical Oncology 2006; 24: 16–24.
• Rini BI, Wilding G, Hudes G, Stadler WM, Kim S, Tarazi J, Rosbrook B, Trask PC, Wood L & Dutcher JP. Phase II study of axitinib in sorafenib-refram, ctory metastatic renal cell carcinoma. Journal of Clinical Oncology 2009;
• 27: 4462–4468.
• Hartmann JT, Haap M, Kopp HG & Lipp HP. Tyrosine kinase inhibitors –a review on pharmacology, metabolism and side effects. Current Drug Metabolism 2009; 10: 470–481.
• Fujiwara Y, Kiyota N, Chayahara N, Suzuki A, Umeyama Y, Mukohara T, Minami H. Management of axitinib (AG-013736)-induced fatigue and thyroid dysfunction, and predictive biomarkers of axitinib exposure: results from phase I studies in Japanese patients. Investigational New Drugs 2012; 30: 1055–1064.
• Robert J. Motzer, M.D., Thomas E. Hutson, D.O. et al. Pazopanib versus Sunitinib in Metastatic Renal-Cell Carcinoma N Engl J Med 2013; 369:722- 731.
• Rini BI, Tamaskar I, Shaheen P, Salas R, Garcia J, Wood L, Reddy S, Dreicer R,Bukowski RM. Hypothyroidism in patients with metastatic renal cell carcinoma treated with sunitinib. Journal of the National Cancer Institute
• 2007; 99: 81–83.
• Schmidinger M, Vogl UM, Bojic M, Lamm W, Heinzl H, Haitel A, Clodi M, Kramer G, Zielinski CC. Hypothyroidism in patients with renal cell
• carcinoma: blessing or curse? Cancer 2011; 117: 534–544.
• Rini BI, Escudier B, Tomczak P, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet 2011; 378: 1931–1939.
• Sternberg CN, Davis ID, Mardiak J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. Journal of Clinical Oncology 2010; 28: 1061–1068
• Wolter P, StefanC,Decallonne B,DumezH, Bex M, Carmeliet P, Schoffski P. The clinical implications of sunitinib-induced hypothyroidism: a prospective evaluation. British Journal of Cancer 2008; 99: 448–454.
• Clemons J, Gao D, NaamM, Breaker K, Garfield D, Flaig TW. Thyroid dysfunction in patients treated with sunitinib or sorafenib. Clinical
• Genitourinary Cancer 2012; 10: 225–231.
• Sella A, Hercbergs AH, Hanovich E, Kovel S. Does sunitinib-induced hypothyroidism play a role in the activity of sunitinib in metastatic renal cell carcinoma? Chemotherapy 2012; 58: 200–205.
• Sabatier R, Eymard JC, Walz J, et al. Could thyroid dysfunction influence outcome in sunitinib-treated metastatic renal cell carcinoma? Annals of Oncology 2012; 23: 714–721.
• Sakurai K, Fukazawa H, Arihara Z, Yoshida K. Sunitinib-induced thyrotoxicosis followed by persistent hypothyroidism with shrinkage of
• thyroid volume. Tohoku J Exp Med 2010; 222: 39-44.
• Piñar D, Boix E, Meana JA, Herrero J. Sunitinib-induced thyrotoxicosis. J Endocrinol Invest 2009; 32: 941-2.
• Jazvi􀀀 M, Prpi􀀀 M, Juki􀀀 T, et al. Sunitinib-induced thyrotoxicosis - a not so rare entity. Anticancer Res 2015; 35: 481-5.
• Cinemre H, Bilir C, Gokosmanoglu F, Akdemir N, Erdogmus B, Buyukkaya R. Predictors of time to remission and treatment failure in patients with Graves' disease treated with propylthiouracil. Clin Invest Med 2009; 32:
• 199-205.
• Bilir C, Gökosmanoglu F, Caliskan M, Cinemre H, Akdemir R. Regression of the carotid intima media thickness by propylthiouracil therapy in Graves' hyperthyroidism. Am J Med Sci 2012 ; 343: 273-6.