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Horm Metab Res 2021; 53(12): 794-800
DOI: 10.1055/a-1658-3077
Endocrine Care

Sunitinib-Induced Hypothyroidism and Survival in Pancreatic Neuroendocrine Tumors

Annie Mathew
1   Department of Endocrinology, Diabetes and Metabolism and Division of Laboratory Research, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
,
Dagmar Führer
1   Department of Endocrinology, Diabetes and Metabolism and Division of Laboratory Research, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
,
Harald Lahner
1   Department of Endocrinology, Diabetes and Metabolism and Division of Laboratory Research, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
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Abstract

Sunitinib has been approved for the treatment of pancreatic neuroendocrine tumors, renal-cell carcinoma, and gastrointestinal stromal tumors. The elevation of thyroid-stimulating hormone serum levels is a common side effect. Studies suggest a correlation between sunitinib-induced hypothyroidism and treatment outcome in patients with renal-cell carcinoma and gastrointestinal stromal tumors. This study assessed whether sunitinib-induced hypothyroidism is a predictive marker of the objective response rate, progression-free survival, and overall survival in pancreatic neuroendocrine tumor patients. Twenty-nine patients treated with sunitinib for advanced pancreatic neuroendocrine tumors were included. The incidence of sunitinib-induced hypothyroidism was 33%. The median progression-free survival of patients who developed hypothyroidism was 16 months (95% confidence interval: 6.2–25.8 months) as compared with six months among euthyroid patients (95% confidence interval: 0.1–12.2 months) (p=0.02). The median overall survival was 77 months (95% confidence interval: 31.4–122.6 months) in hypothyroid patients but 12 months (95% confidence interval: 5.9–18.1 months) in subjects with euthyroidism (p=0.001). The median overall survival from the time of initial diagnosis ranged from 247 months in patients with hypothyroidism to 65 months in euthyroid subjects (p=0.015). Elevated thyroid-stimulating hormone levels are a prognostic biomarker of improved outcomes of sunitinib therapy in pancreatic neuroendocrine tumor patients.

Key words

pancreatic neuroendocrine tumor - neuroendocrinology - predictive factor - tyrosine kinase inhibitor - survival


Publication History

Received: 06 August 2021

Accepted after revision: 26 September 2021

Article published online:
10 December 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Dasari A, Shen C, Halperin D. et al Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States. JAMA Oncol 2017; 3: 1335-1342
    CrossrefPubMedGoogle Scholar
  • 2 Falconi M, Eriksson B, Kaltsas G. et al ENETS consensus guidelines update for the management of patients with functional pancreatic neuroendocrine tumors and non-functional pancreatic neuroendocrine tumors. Neuroendocrinology 2016; 103: 153-171
    CrossrefPubMedGoogle Scholar
  • 3 Panzuto F, Boninsegna L, Fazio N. et al Metastatic and locally advanced pancreatic endocrine carcinomas: Analysis of factors associated with disease progression. J Clin Oncol 2011; 29: 2372-2377
    CrossrefPubMedGoogle Scholar
  • 4 Halfdanarson TR, Strosberg JR, Tang L. et al The North American neuroendocrine tumor society consensus guidelines for surveillance and medical management of pancreatic neuroendocrine tumors. Pancreas 2020; 49: 863-881
    CrossrefPubMedGoogle Scholar
  • 5 Desai J, Yassa L, Marqusee E. et al Hypothyroidism after sunitinib treatment for patients with gastrointestinal stromal tumors. Ann Intern Med 2006; 145: 660-664
    CrossrefPubMedGoogle Scholar
  • 6 Rini BI, Tamaskar I, Shaheen P. et al Hypothyroidism in patients with metastatic renal cell carcinoma treated with sunitinib. J Natl Cancer Inst 2007; 99: 81-83
    CrossrefPubMedGoogle Scholar
  • 7 Kappers MH, van Esch JH, Smedts FM. et al Sunitinib-induced hypothyroidism is due to induction of type 3 deiodinase activity and thyroidal capillary regression. J Clin Endocrinol Metab 2011; 96: 3087-3094
    CrossrefPubMedGoogle Scholar
  • 8 Mannavola D, Coco P, Vannucchi G. et al A novel tyrosine-kinase selective inhibitor, sunitinib, induces transient hypothyroidism by blocking iodine uptake. J Clin Endocrinol Metab 2007; 92: 3531-3534
    CrossrefPubMedGoogle Scholar
  • 9 Wong E, Rosen LS, Mulay M. et al Sunitinib induces hypothyroidism in advanced cancer patients and may inhibit thyroid peroxidase activity. Thyroid 2007; 17: 351-355
    CrossrefPubMedGoogle Scholar
  • 10 Baldazzi V, Tassi R, Lapini A. et al The impact of sunitinib-induced hypothyroidism on progression-free survival of metastatic renal cancer patients: A prospective single-center study. Urol Oncol 2012; 30: 704-710
    CrossrefPubMedGoogle Scholar
  • 11 Riesenbeck LM, Bierer S, Hoffmeister I. et al Hypothyroidism correlates with a better prognosis in metastatic renal cancer patients treated with sorafenib or sunitinib. World J Urol 2011; 29: 807-813
    CrossrefPubMedGoogle Scholar
  • 12 Sabatier R, Eymard JC, Walz J. et al Could thyroid dysfunction influence outcome in sunitinib-treated metastatic renal cell carcinoma?. Ann Oncol 2012; 23: 714-721
    CrossrefPubMedGoogle Scholar
  • 13 Schmidinger M, Vogl UM, Bojic M. et al Hypothyroidism in patients with renal cell carcinoma: blessing or curse?. Cancer 2011; 117: 534-544
    CrossrefPubMedGoogle Scholar
  • 14 Sella A, Hercbergs AH, Hanovich E. et al Does sunitinib-induced hypothyroidism play a role in the activity of sunitinib in metastatic renal cell carcinoma?. Chemotherapy 2012; 58: 200-205
    CrossrefPubMedGoogle Scholar
  • 15 Vasileiadis T, Chrisofos M, Safioleas M. et al Iotampact of sunitinib-induced hypothyroidism on survival of patients with metastatic renal cancer. BMC Cancer 2019; 19: 407
    CrossrefPubMedGoogle Scholar
  • 16 Lloyd RV, Klöppel G, Rosai J. WHO Classification of Tumours of Endocrine Organs. IARC Press; 2017
    Google Scholar
  • 17 Garber JR, Cobin RH, Gharib H. et al Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American association of clinical endocrinologists and the American thyroid association. Endocr Pract 2012; 18: 988-1028
    CrossrefPubMedGoogle Scholar
  • 18 Bozkurt O, Karaca H, Hacibekiroglu I. et al Is sunitinib-induced hypothyroidism a predictive clinical marker for better response in metastatic renal cell carcinoma patients?. J Chemother 2016; 28: 230-234
    CrossrefPubMedGoogle Scholar
  • 19 Raymond E, Dahan L, Raoul JL. et al Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med 2011; 364: 501-513
    CrossrefPubMedGoogle Scholar
  • 20 Buda-Nowak A, Kucharz J, Dumnicka P. et al Sunitinib-induced hypothyroidism predicts progression-free survival in metastatic renal cell carcinoma patients. Med Oncol 2017; 34: 68
    CrossrefPubMedGoogle Scholar
  • 21 Wolter P, Stefan C, Decallonne B. et al The clinical implications of sunitinib-induced hypothyroidism: a prospective evaluation. Br J Cancer 2008; 99: 448-454
    CrossrefPubMedGoogle Scholar
  • 22 Latteyer S, Christoph S, Theurer S. et al Thyroxine promotes lung cancer growth in an orthotopic mouse model. Endocr Relat Cancer 2019; 26: 565-574
    CrossrefPubMedGoogle Scholar
  • 23 Hercbergs A, Davis PJ, Lin HY. et al Possible contributions of thyroid hormone replacement to specific behaviors of cancer. Biomed Pharmacother 2016; 84: 655-659
    CrossrefPubMedGoogle Scholar
  • 24 Shinohara N, Takahashi M, Kamishima T. et al The incidence and mechanism of sunitinib-induced thyroid atrophy in patients with metastatic renal cell carcinoma. Br J Cancer 2011; 104: 241-247
    CrossrefPubMedGoogle Scholar