Endocrine complications of modern cancer therapy

Czech version

Authors: Jan Čáp
Authors‘ workplace: IV. interní hematologická klinika LF UK a FN Hradec Králové
Published in: Vnitř Lék 2016; 62(Suppl 3): 45-49
Category: Reviews

Overview

Treatment with tyrosine kinase inhibitors leads to thyroid dysfunction in up to one half of treated patients, hypothyroidism being the most common. It is caused by destructive thyroiditis, impaired transport of T₄ into the cell and deiodinase induction. Bexarotene is a nuclear retinoid X receptor agonist. Its application is accompanied with central hypothyroidism and hypertriglyceriaemia in virtually all patients and it also increases thyroxin metabolism. Autoimmune endocrine side effects are common in cancer immunotherapy. Cytokines (interpheron α and interleukin 2) cause autoimmune thyroiditis in 2–10 % of treated patients. Therapy with immune checkpoints inhibitors is connected with a variety of immune-related adverse events (irAE). Endocrine irAE include hypophysitis and thyroiditis during treatment with monoclonal antibodies against CTLA4 and thyroid dysfunction during therapy with antibody against CD1 receptor and its ligand. Knowledge, early recognition and management of these side effects is crucial.

Key words:
bexarotene – endocrine complication – hypophysitis – immune checkpoint inhibitors – immunotherapy

Sources

1. Croce CM. Oncogenes and cancer. N Engl J Med 2008; 358(5): 502–511. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMra072367>.

2. Abdel-Rahman O, Fouad M. Efficacy and toxicity of sunitinib for non clear cell renal cell carcinoma (RCC): a systematic review of the literature. Crit Rev Oncol Hematol 2015; 94(2): 238–250. Dostupné z DOI: <http://dx.doi.org/10.1016/j.critrevonc.2015.01.006>.

3. Desai J, Yassa L, Marqusee E et al. Hypothyroidism after sunitinib treatment for patients with gastrointestinal stromal tumors. Ann Intern Med 2006; 145(9): 660–664.

4. 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(9): 3531–3534.

5. Wolter P, Stefan C, Decallonne B et al. The clinical implications of sunitinib-induced hypothyroidism: a prospective evaluation. Br J Cancer 2008; 99(3): 448–454. Dostupné z DOI: <http://dx.doi.org/10.1038/sj.bjc.6604497>.

6. Raymond E, Dahan L, Raoul JL et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med 2011; 364(6): 501–513. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1003825>.

7. Braun D, Kim TD, le Coutre P et al. Tyrosine kinase inhibitors noncompetitively inhibit MCT8-mediated iodothyronine transport. J Clin Endocrinol Metab 2012; 97(1): E100-E105. Dostupné z DOI: <http://dx.doi.org/10.1210/jc.2011–1837>.

8. 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(10): 3087–3094. Dostupné z DOI: <http://dx.doi.org/10.1210/jc.2011–1172>.

9. Blair HA, Plosker GL. Sorafenib: a review of its use in patients with radioactive iodine-refractory, metastatic differentiated thyroid carcinoma. Target Oncol 2015; 10(1): 171–178. Dostupné z DOI: <http://dx.doi.org/10.1007/s11523–015–0363-z>.

10. Feldt S, Schussel K, Quinzler R et al Incidence of thyroid hormone therapy in patients treated with sunitinib or sorafenib: a cohort study. Eur J Cancer 2012; 48(7): 974–981. Dostupné z DOI: <http://dx.doi.org/10.1016/j.ejca.2012.01.036>.

11. Clemons J, Gao D, Naam M et al. Thyroid dysfunction in patients treated with sunitinib or sorafenib. Clin Genitourin Cancer 2012; 10(4): 225–231. Dostupné z DOI: <http://dx.doi.org/10.1016/j.clgc.2012.08.002>.

12. Illouz F, Braun D, Briet C et al. Endocrine side-effects of anti-cancer drugs: thyroid effects of tyrosine kinase inhibitors. Eur J Endocrinol 2014; 171(3): R91-R99. Dostupné z DOI: <http://dx.doi.org/10.1530/EJE-14–0198>.

13. Cooper MR, Yi SY, Alghamdi W et al. Vandetanib for the treatment of medullary thyroid carcinoma. Ann Pharmacother 2014; 48(3): 387–394. Dostupné z DOI: <http://dx.doi.org/10.1177/1060028013512791>.

14. Verloop H, Smit JW, Dekkers OM. Sorafenib therapy decreases the clearance of thyrotropin. Eur J Endocrinol 2013; 168(2): 163–167. Dostupné z DOI: <http://dx.doi.org/10.1530/EJE-12–0828>.

15. Qi L, Guo Y, Zhang P et al. Preventive and Therapeutic Effects of the Retinoid X Receptor Agonist Bexarotene on Tumors. Curr Drug Metab 2016; 17(2): 118–128.

16. Sherman SI, Gopal J, Haugen BR et al. Central hypothyroidism associated with retinoid X receptor-selective ligands. N Engl J Med 1999; 340(14): 1075–1079.

17. Graeppi-Dulac J, Vlaeminck-Guillem V, Perier-Muzet M et al. Endocrine side-effects of anti-cancer drugs: the impact of retinoids on the thyroid axis. Eur J Endocrinol 2014; 170(6): R253-R262. Dostupné z DOI: <http://dx.doi.org/10.1530/EJE-13–0920>.

18. Liu S, Ogilvie KM, Klausing K et al. Mechanism of selective retinoid X receptor agonist-induced hypothyroidism in the rat. Endocrinology 2002; 143(8): 2880–2885.

19. Smit JW, Stokkel MP, Pereira AM et al. Bexarotene-induced hypothyroidism: bexarotene stimulates the peripheral metabolism of thyroid hormones. J Clin Endocrinol Metab 2007; 92(7): 2496–2499.

20. Sharma V, Hays WR, Wood WM et al. Effects of rexinoids on thyrotrope function and the hypothalamic-pituitary-thyroid axis. Endocrinology 2006; 147(3): 1438–1451.

21. Scarisbrick JJ, Morris S, Azurdia R et al. U.K. consensus statement on safe clinical prescribing of bexarotene for patients with cutaneous T-cell lymphoma. Br J Dermatol 2013; 168(1): 192–200. Dostupné z DOI: <http://dx.doi.org/10.1111/bjd.12042>.

22. Tomer Y, Blackard JT, Akeno N. Interferon alpha treatment and thyroid dysfunction. Endocrinol Metab Clin North Am 2007; 36(4): 1051–1066; x-xi.

23. Hamnvik OP, Larsen PR, Marqusee E. Thyroid dysfunction from antineoplastic agents. J Natl Cancer Inst 2011; 103(21): 1572–1587. Dostupné z DOI: <http://dx.doi.org/10.1093/jnci/djr373>.

24. Ward DL, Bing-You RG. Autoimmune thyroid dysfunction induced by interferon-alpha treatment for chronic hepatitis C: screening and monitoring recommendations. Endocr Pract 2001; 7(1): 52–58.

25. Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature 2011; 480(7378): 480–489. Dostupné z DOI: <http://dx.doi.org/10.1038/nature10673>.

26. Faje A. Immunotherapy and hypophysitis: clinical presentation, treatment, and biologic insights. Pituitary 2016; 19(1): 82–92. Dostupné z DOI: <http://dx.doi.org/10.1007/s11102–015–0671–4>.

27. Eggermont AM, Chiarion-Sileni V, Grob JJ et al. Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial. Lancet Oncol 2015; 16(5): 522–530. Dostupné z DOI: <http://dx.doi.org/10.1016/S1470–2045(15)70122–1>.

28. Dillard T, Yedinak CG, Alumkal J et al. Anti-CTLA-4 antibody therapy associated autoimmune hypophysitis: serious immune related adverse events across a spectrum of cancer subtypes. Pituitary 2010; 13(1): 29–38. Dostupné z DOI: <http://dx.doi.org/10.1007/s11102–009–0193-z>.

29. Ryder M, Callahan M, Postow MA et al. Endocrine-related adverse events following ipilimumab in patients with advanced melanoma: a comprehensive retrospective review from a single institution. Endocr Relat Cancer 2014; 21(2): 371–381. Dostupné z DOI: <http://dx.doi.org/10.1530/ERC-13–0499>.

30. Ribas A, Camacho LH, Lopez-Berestein G et al. Antitumor activity in melanoma and anti-self responses in a phase I trial with the anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody CP-675,206. J Clin Oncol 2005; 23(35): 8968–8977.

31. Albarel F, Gaudy C, Castinetti F et al. Long-term follow-up of ipilimumab-induced hypophysitis, a common adverse event of the anti-CTLA-4 antibody in melanoma. Eur J Endocrinol 2015; 172(2): 195–204. Dostupné z DOI: <http://dx.doi.org/10.1530/EJE-14–0845>.

32. Faje AT, Sullivan R, Lawrence D et al. Ipilimumab-induced hypophysitis: a detailed longitudinal analysis in a large cohort of patients with metastatic melanoma. J Clin Endocrinol Metab 2014; 99(11): 4078–4085. Dostupné z DOI: <http://dx.doi.org/10.1210/jc.2014–2306>.

33. Min L, Hodi FS, Giobbie-Hurder A et al. Systemic high-dose corticosteroid treatment does not improve the outcome of ipilimumab-related hypophysitis: a retrospective cohort study. Clin Cancer Res 2015; 21(4): 749–755. Dostupné z DOI: <http://dx.doi.org/10.1158/1078–0432.CCR-14–2353>.

34. Joshi MN, Whitelaw BC, Palomar MT et al. Immune checkpoint inhibitor related hypophysitis and endocrine dysfunction: Clinical Review. Clin Endocrinol (Oxf) 2016; 85(3): 331–339. Dostupné z DOI: <http://dx.doi.org/10.1111/cen.13063>.

35. Yoshida T, Nakayama M, Suzuki O et al. Salvage radiotherapy for prostate-specific antigen relapse after radical prostatectomy for prostate cancer: a single-center experience. Jpn J Clin Oncol 2011; 41(8): 1031–1036. Dostupné z DOI: <http://dx.doi.org/10.1093/jjco/hyr078>.

36. Torino F, Corsello SM, Salvatori R. Endocrinological side-effects of immune checkpoint inhibitors. Curr Opin Oncol 2016; 28(4): 278–287. Dostupné z DOI: <http://dx.doi.org/10.1097/CCO.0000000000000293>.

37. Keir ME, Butte MJ, Freeman GJ et al. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol 2008; 26: 677–704. Dostupné z DOI: <http://dx.doi.org/10.1146/annurev.immunol.26.021607.090331>.

38. Topalian SL, Drake CG, Pardoll DM. Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity. Curr Opin Immunol 2012; 24(2): 207–212. Dostupné z DOI: <http://dx.doi.org/10.1016/j.coi.2011.12.009>.

39. Garon EB, Rizvi NA, Hui R et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 2015; 372(21): 2018–2028. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1501824>.

40. Hamid O, Robert C, Daud A et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med 2013; 369(2): 134–144. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1305133>.

41. Robert C, Ribas A, Wolchok JD et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet 2014; 384(9948): 1109–1117. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140–6736(14)60958–2>.

42. Topalian SL, Sznol M, McDermott DF et al. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol 2014; 32(10): 1020–1030. Dostupné z DOI: <http://dx.doi.org/10.1200/JCO.2013.53.0105>.

43. Gonzalez-Rodriguez E, Rodriguez-Abreu D. [Spanish Group for Cancer Immuno-Biotherapy (GETICA)]. Immune Checkpoint Inhibitors: Review and Management of Endocrine Adverse Events. Oncologist 2016; 21(7): 804–816. Dostupné z DOI: <http://dx.doi.org/10.1634/theoncologist.2015–0509>.

44. Sul J, Blumenthal GM, Jiang X et al. FDA Approval Summary: Pembrolizumab for the Treatment of Patients With Metastatic Non-Small Cell Lung Cancer Whose Tumors Express Programmed Death-Ligand 1. Oncologist 2016; 21(5): 643–650. Dostupné z DOI: <http://dx.doi.org/10.1634/theoncologist.2015–0498>.

45. McDermott DF, Sosman JA, Sznol M et al. Atezolizumab, an Anti-Programmed Death-Ligand 1 Antibody, in Metastatic Renal Cell Carcinoma: Long-Term Safety, Clinical Activity, and Immune Correlates From a Phase Ia Study. J Clin Oncol 2016; 34(8): 833–842. Dostupné z DOI: <http://dx.doi.org/10.1200/JCO.2015.63.7421>.

46. Antonia S, Goldberg SB, Balmanoukian A et al. Safety and antitumour activity of durvalumab plus tremelimumab in non-small cell lung cancer: a multicentre, phase 1b study. Lancet Oncol 2016; 17(3): 299–308. Dostupné z DOI: <http://dx.doi.org/10.1016/S1470–2045(15)00544–6>.

47. Larkin J, Chiarion-Sileni V, Gonzalez R et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med 2015; 373(1): 23–34. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1504030>.

48. Antonia SJ, Lopez-Martin JA, Bendell J et al. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol 2016; 17(17): 883–895. Dostupné z DOI: <http://dx.doi.org/10.1016/S1470–2045(16)30098–5>.

49. Weber JS, Postow M, Lao CD et al. Management of Adverse Events Following Treatment With Anti-Programmed Death-1 Agents. Oncologist 2016; PMID: 27401894. Dostupné z DOI: <http://dx.doi.org/10.1634/theoncologist.2016–0055>.

50. Champiat S, Lambotte O, Barreau E et al. Management of immune checkpoint blockade dysimmune toxicities: a collaborative position paper. Ann Oncol 2016; 27(4): 559–574. Dostupné z DOI: <http://dx.doi.org/10.1093/annonc/mdv623>.