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Targeted Oncology

, Volume 10, Issue 3, pp 311–324 | Cite as

Treatment of advanced thyroid cancer: role of molecularly targeted therapies

  • Lorinda L. Covell
  • Apar Kishor GantiEmail author
Review

Abstract

Advanced thyroid cancer is not amenable to therapy with conventional cytotoxic chemotherapy. However, newer advances in the understanding of the molecular pathogenesis of different subtypes of thyroid cancer have provided new opportunities for the evaluation of molecularly targeted therapies. This has led to multiple clinical trials using various multi-kinase inhibitors and the subsequent US FDA approval of sorafenib for differentiated thyroid cancer and vandetanib and cabozantinib for medullary thyroid carcinoma. This review provides a summary of the current literature for the treatment of advanced thyroid carcinoma and future directions in this disease.

Keywords

Molecularly targeted therapies Multi-kinase inhibitors Thyroid cancer 

Notes

Conflict of interest

Dr. Covell has nothing to disclose. Dr. Ganti reports personal fees from Boehringer Ingelheim, Otsuka Pharmaceuticals, and Biodesix, Inc, outside the submitted work.

References

  1. 1.
    Siegel R, Ma J, Zou Z, Jemal A (2014) Cancer statistics, 2014. CA Cancer J Clin 64(1):9–29. doi: 10.3322/caac.21208 CrossRefPubMedGoogle Scholar
  2. 2.
    Olaleye O, Ekrikpo U, Moorthy R, Lyne O, Wiseberg J, Black M, Mitchell D (2011) Increasing incidence of differentiated thyroid cancer in South East England: 1987-2006. Eur Arch Otorhinolaryngol Off J Eur Fed Otorhinolaryngol Soc 268(6):899–906. doi: 10.1007/s00405-010-1416-7 CrossRefGoogle Scholar
  3. 3.
    Cramer JD, Fu P, Harth KC, Margevicius S, Wilhelm SM (2010) Analysis of the rising incidence of thyroid cancer using the Surveillance, Epidemiology and End Results national cancer data registry. Surgery 148(6):1147–1152. doi: 10.1016/j.surg.2010.10.016, discussion 1152-1143CrossRefPubMedGoogle Scholar
  4. 4.
    Kilfoy BA, Zheng T, Holford TR, Han X, Ward MH, Sjodin A, Zhang Y, Bai Y, Zhu C, Guo GL, Rothman N, Zhang Y (2009) International patterns and trends in thyroid cancer incidence, 1973-2002. Cancer Causes Control CCC 20(5):525–531. doi: 10.1007/s10552-008-9260-4 PubMedCentralCrossRefPubMedGoogle Scholar
  5. 5.
    Enewold L, Zhu K, Ron E, Marrogi AJ, Stojadinovic A, Peoples GE, Devesa SS (2009) Rising thyroid cancer incidence in the United States by demographic and tumor characteristics, 1980-2005. Cancer Epidemiol Biomarkers Prev Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol 18(3):784–791. doi: 10.1158/1055-9965.EPI-08-0960 CrossRefGoogle Scholar
  6. 6.
    Modigliani E, Cohen R, Campos JM, Conte-Devolx B, Maes B, Boneu A, Schlumberger M, Bigorgne JC, Dumontier P, Leclerc L, Corcuff B, Guilhem I (1998) Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: results in 899 patients. The GETC Study Group. Groupe d’etude des tumeurs a calcitonine. Clin Endocrinol 48(3):265–273CrossRefGoogle Scholar
  7. 7.
    Hundahl SA, Fleming ID, Fremgen AM, Menck HR (1998) A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985-1995 [see comments]. Cancer 83(12):2638–2648CrossRefPubMedGoogle Scholar
  8. 8.
    Sherman SI (2003) Thyroid carcinoma. Lancet 361(9356):501–511CrossRefPubMedGoogle Scholar
  9. 9.
    Ronga G, Filesi M, Montesano T, Di Nicola AD, Pace C, Travascio L, Ventroni G, Antonaci A, Vestri AR (2004) Lung metastases from differentiated thyroid carcinoma. A 40 years’ experience. Q J Nucl Med Mol Imaging Off Publ Ital Assoc Nucl Med 48(1):12–19Google Scholar
  10. 10.
    Kondo T, Ezzat S, Asa SL (2006) Pathogenetic mechanisms in thyroid follicular-cell neoplasia. Nat Rev Cancer 6(4):292–306. doi: 10.1038/nrc1836 CrossRefPubMedGoogle Scholar
  11. 11.
    Sherman SI (2010) Cytotoxic chemotherapy for differentiated thyroid carcinoma. Clin Oncol 22(6):464–468. doi: 10.1016/j.clon.2010.03.014 CrossRefGoogle Scholar
  12. 12.
    Fagin JA, Mitsiades N (2008) Molecular pathology of thyroid cancer: diagnostic and clinical implications. Best Pract Res Clin Endocrinol Metab 22(6):955–969. doi: 10.1016/j.beem.2008.09.017 PubMedCentralCrossRefPubMedGoogle Scholar
  13. 13.
    Takahashi M, Buma Y, Iwamoto T, Inaguma Y, Ikeda H, Hiai H (1988) Cloning and expression of the ret proto-oncogene encoding a tyrosine kinase with two potential transmembrane domains. Oncogene 3(5):571–578PubMedGoogle Scholar
  14. 14.
    Runeberg-Roos P, Saarma M (2007) Neurotrophic factor receptor RET: structure, cell biology, and inherited diseases. Ann Med 39(8):572–580. doi: 10.1080/07853890701646256 CrossRefPubMedGoogle Scholar
  15. 15.
    Elisei R, Cosci B, Romei C, Bottici V, Renzini G, Molinaro E, Agate L, Vivaldi A, Faviana P, Basolo F, Miccoli P, Berti P, Pacini F, Pinchera A (2008) Prognostic significance of somatic RET oncogene mutations in sporadic medullary thyroid cancer: a 10-year follow-up study. J Clin Endocrinol Metab 93(3):682–687. doi: 10.1210/jc.2007-1714 CrossRefPubMedGoogle Scholar
  16. 16.
    Mulligan LM, Eng C, Healey CS, Clayton D, Kwok JB, Gardner E, Ponder MA, Frilling A, Jackson CE, Lehnert H et al (1994) Specific mutations of the RET proto-oncogene are related to disease phenotype in MEN 2A and FMTC. Nat Genet 6(1):70–74. doi: 10.1038/ng0194-70 CrossRefPubMedGoogle Scholar
  17. 17.
    Moura MM, Cavaco BM, Pinto AE, Domingues R, Santos JR, Cid MO, Bugalho MJ, Leite V (2009) Correlation of RET somatic mutations with clinicopathological features in sporadic medullary thyroid carcinomas. Br J Cancer 100(11):1777–1783. doi: 10.1038/sj.bjc.6605056 PubMedCentralCrossRefPubMedGoogle Scholar
  18. 18.
    Kimura ET, Nikiforova MN, Zhu Z, Knauf JA, Nikiforov YE, Fagin JA (2003) High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma. Cancer Res 63(7):1454–1457PubMedGoogle Scholar
  19. 19.
    Meinkoth JL (2004) Biology of Ras in thyroid cells. Cancer Treat Res 122:131–148CrossRefPubMedGoogle Scholar
  20. 20.
    Smallridge RC, Marlow LA, Copland JA (2009) Anaplastic thyroid cancer: molecular pathogenesis and emerging therapies. Endocr Relat Cancer 16(1):17–44. doi: 10.1677/ERC-08-0154 PubMedCentralCrossRefPubMedGoogle Scholar
  21. 21.
    Ciampi R, Nikiforov YE (2007) RET/PTC rearrangements and BRAF mutations in thyroid tumorigenesis. Endocrinology 148(3):936–941. doi: 10.1210/en.2006-0921 CrossRefPubMedGoogle Scholar
  22. 22.
    Kebebew E, Weng J, Bauer J, Ranvier G, Clark OH, Duh QY, Shibru D, Bastian B, Griffin A (2007) The prevalence and prognostic value of BRAF mutation in thyroid cancer. Ann Surg 246(3):466–470. doi: 10.1097/SLA.0b013e318148563d, discussion 470-461PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.
    Xing M (2005) BRAF mutation in thyroid cancer. Endocr Relat Cancer 12(2):245–262. doi: 10.1677/erc.1.0978 CrossRefPubMedGoogle Scholar
  24. 24.
    Elisei R, Ugolini C, Viola D, Lupi C, Biagini A, Giannini R, Romei C, Miccoli P, Pinchera A, Basolo F (2008) BRAF(V600E) mutation and outcome of patients with papillary thyroid carcinoma: a 15-year median follow-up study. J Clin Endocrinol Metab 93(10):3943–3949. doi: 10.1210/jc.2008-0607 CrossRefPubMedGoogle Scholar
  25. 25.
    Nikiforova MN, Kimura ET, Gandhi M, Biddinger PW, Knauf JA, Basolo F, Zhu Z, Giannini R, Salvatore G, Fusco A, Santoro M, Fagin JA, Nikiforov YE (2003) BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. J Clin Endocrinol Metab 88(11):5399–5404. doi: 10.1210/jc.2003-030838 CrossRefPubMedGoogle Scholar
  26. 26.
    Saji M, Ringel MD (2010) The PI3K-Akt-mTOR pathway in initiation and progression of thyroid tumors. Mol Cell Endocrinol 321(1):20–28. doi: 10.1016/j.mce.2009.10.016 PubMedCentralCrossRefPubMedGoogle Scholar
  27. 27.
    Ricarte-Filho JC, Ryder M, Chitale DA, Rivera M, Heguy A, Ladanyi M, Janakiraman M, Solit D, Knauf JA, Tuttle RM, Ghossein RA, Fagin JA (2009) Mutational profile of advanced primary and metastatic radioactive iodine-refractory thyroid cancers reveals distinct pathogenetic roles for BRAF, PIK3CA, and AKT1. Cancer Res 69(11):4885–4893. doi: 10.1158/0008-5472.CAN-09-0727 PubMedCentralCrossRefPubMedGoogle Scholar
  28. 28.
    Bruni P, Boccia A, Baldassarre G, Trapasso F, Santoro M, Chiappetta G, Fusco A, Viglietto G (2000) PTEN expression is reduced in a subset of sporadic thyroid carcinomas: evidence that PTEN-growth suppressing activity in thyroid cancer cells mediated by p27kip1. Oncogene 19(28):3146–3155. doi: 10.1038/sj.onc.1203633 CrossRefPubMedGoogle Scholar
  29. 29.
    Dahia PL, Marsh DJ, Zheng Z, Zedenius J, Komminoth P, Frisk T, Wallin G, Parsons R, Longy M, Larsson C, Eng C (1997) Somatic deletions and mutations in the Cowden disease gene, PTEN, in sporadic thyroid tumors. Cancer Res 57(21):4710–4713PubMedGoogle Scholar
  30. 30.
    Ferrara N, Kerbel RS (2005) Angiogenesis as a therapeutic target. Nature 438(7070):967–974. doi: 10.1038/nature04483 CrossRefPubMedGoogle Scholar
  31. 31.
    Espinosa AV, Porchia L, Ringel MD (2007) Targeting BRAF in thyroid cancer. Br J Cancer 96(1):16–20. doi: 10.1038/sj.bjc.6603520 PubMedCentralCrossRefPubMedGoogle Scholar
  32. 32.
    Lin JD, Chao TC (2005) Vascular endothelial growth factor in thyroid cancers. Cancer Biother Radiopharm 20(6):648–661. doi: 10.1089/cbr.2005.20.648 CrossRefPubMedGoogle Scholar
  33. 33.
    Capp C, Wajner SM, Siqueira DR, Brasil BA, Meurer L, Maia AL (2010) Increased expression of vascular endothelial growth factor and its receptors, VEGFR-1 and VEGFR-2, in medullary thyroid carcinoma. Thyroid Off J Am Thyroid Assoc 20(8):863–871. doi: 10.1089/thy.2009.0417 CrossRefGoogle Scholar
  34. 34.
    Viglietto G, Maglione D, Rambaldi M, Cerutti J, Romano A, Trapasso F, Fedele M, Ippolito P, Chiappetta G, Botti G et al (1995) Upregulation of vascular endothelial growth factor (VEGF) and downregulation of placenta growth factor (PlGF) associated with malignancy in human thyroid tumors and cell lines. Oncogene 11(8):1569–1579PubMedGoogle Scholar
  35. 35.
    Gupta-Abramson V, Troxel AB, Nellore A, Puttaswamy K, Redlinger M, Ransone K, Mandel SJ, Flaherty KT, Loevner LA, O’Dwyer PJ, Brose MS (2008) Phase II trial of sorafenib in advanced thyroid cancer. J Clin Oncol Off J Am Soc Clin Oncol 26(29):4714–4719. doi: 10.1200/JCO.2008.16.3279 CrossRefGoogle Scholar
  36. 36.
    Kloos RT, Ringel MD, Knopp MV, Hall NC, King M, Stevens R, Liang J, Wakely PE Jr, Vasko VV, Saji M, Rittenberry J, Wei L, Arbogast D, Collamore M, Wright JJ, Grever M, Shah MH (2009) Phase II trial of sorafenib in metastatic thyroid cancer. J Clin Oncol Off J Am Soc Clin Oncol 27(10):1675–1684. doi: 10.1200/JCO.2008.18.2717 CrossRefGoogle Scholar
  37. 37.
    Hoftijzer H, Heemstra KA, Morreau H, Stokkel MP, Corssmit EP, Gelderblom H, Weijers K, Pereira AM, Huijberts M, Kapiteijn E, Romijn JA, Smit JW (2009) Beneficial effects of sorafenib on tumor progression, but not on radioiodine uptake, in patients with differentiated thyroid carcinoma. Eur J Endocrinol Eur Fed Endocr Soc 161(6):923–931. doi: 10.1530/EJE-09-0702 CrossRefGoogle Scholar
  38. 38.
    Schneider TC, Abdulrahman RM, Corssmit EP, Morreau H, Smit JW, Kapiteijn E (2012) Long-term analysis of the efficacy and tolerability of sorafenib in advanced radio-iodine refractory differentiated thyroid carcinoma: final results of a phase II trial. Eur J Endocrinol Eur Fed Endocr Soc 167(5):643–650. doi: 10.1530/EJE-12-0405 CrossRefGoogle Scholar
  39. 39.
    Ahmed M, Barbachano Y, Riddell A, Hickey J, Newbold KL, Viros A, Harrington KJ, Marais R, Nutting CM (2011) Analysis of the efficacy and toxicity of sorafenib in thyroid cancer: a phase II study in a UK based population. Eur J Endocrinol Eur Fed Endocr Soc 165(2):315–322. doi: 10.1530/EJE-11-0129 CrossRefGoogle Scholar
  40. 40.
    Hong DS, Cabanillas ME, Wheler J, Naing A, Tsimberidou AM, Ye L, Busaidy NL, Waguespack SG, Hernandez M, El Naggar AK, Bidyasar S, Wright J, Sherman SI, Kurzrock R (2011) Inhibition of the Ras/Raf/MEK/ERK and RET kinase pathways with the combination of the multikinase inhibitor sorafenib and the farnesyltransferase inhibitor tipifarnib in medullary and differentiated thyroid malignancies. J Clin Endocrinol Metab 96(4):997–1005. doi: 10.1210/jc.2010-1899 PubMedCentralCrossRefPubMedGoogle Scholar
  41. 41.
    Cohen EE, Needles BM, Cullen KJ, Wong SJ, Wade JL III, Ivy SP, Villaflor VM, Seiwert TY, Nichols K, Vokes EE (2008) Phase 2 study of sunitinib in refractory thyroid cancer. ASCO Meet Abstr 26(15_suppl):6025Google Scholar
  42. 42.
    Carr LL, Mankoff DA, Goulart BH, Eaton KD, Capell PT, Kell EM, Bauman JE, Martins RG (2010) Phase II study of daily sunitinib in FDG-PET-positive, iodine-refractory differentiated thyroid cancer and metastatic medullary carcinoma of the thyroid with functional imaging correlation. Clin Cancer Res Off J Am Assoc Cancer Res 16(21):5260–5268. doi: 10.1158/1078-0432.CCR-10-0994 CrossRefGoogle Scholar
  43. 43.
    Bible KC, Suman VJ, Molina JR, Smallridge RC, Maples WJ, Menefee ME, Rubin J, Sideras K, Morris JC 3rd, McIver B, Burton JK, Webster KP, Bieber C, Traynor AM, Flynn PJ, Goh BC, Tang H, Ivy SP, Erlichman C, Endocrine Malignancies Disease Oriented G, Mayo Clinic Cancer C, Mayo Phase C (2010) Efficacy of pazopanib in progressive, radioiodine-refractory, metastatic differentiated thyroid cancers: results of a phase 2 consortium study. Lancet Oncol 11(10):962–972. doi: 10.1016/S1470-2045(10)70203-5 PubMedCentralCrossRefPubMedGoogle Scholar
  44. 44.
    Cohen EE, Rosen LS, Vokes EE, Kies MS, Forastiere AA, Worden FP, Kane MA, Sherman E, Kim S, Bycott P, Tortorici M, Shalinsky DR, Liau KF, Cohen RB (2008) Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study. J Clin Oncol Off J Am Soc Clin Oncol 26(29):4708–4713. doi: 10.1200/JCO.2007.15.9566 CrossRefGoogle Scholar
  45. 45.
    Leboulleux S, Bastholt L, Krause T, de la Fouchardiere C, Tennvall J, Awada A, Gomez JM, Bonichon F, Leenhardt L, Soufflet C, Licour M, Schlumberger MJ (2012) Vandetanib in locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 2 trial. Lancet Oncol 13(9):897–905. doi: 10.1016/S1470-2045(12)70335-2 CrossRefPubMedGoogle Scholar
  46. 46.
    Sherman SI, Wirth LJ, Droz JP, Hofmann M, Bastholt L, Martins RG, Licitra L, Eschenberg MJ, Sun YN, Juan T, Stepan DE, Schlumberger MJ, Motesanib Thyroid Cancer Study G (2008) Motesanib diphosphate in progressive differentiated thyroid cancer. N Engl J Med 359(1):31–42. doi: 10.1056/NEJMoa075853 CrossRefPubMedGoogle Scholar
  47. 47.
    Lim SM, Chang H, Yoon MJ, Hong YK, Kim H, Chung WY, Park CS, Nam KH, Kang SW, Kim MK, Kim SB, Lee SH, Kim HG, Na II, Kim YS, Choi MY, Kim JG, Park KU, Yun HJ, Kim JH, Cho BC (2013) A multicenter, phase II trial of everolimus in locally advanced or metastatic thyroid cancer of all histologic subtypes. Ann Oncol Off J Eur Soc Med Oncol ESMO 24(12):3089–3094. doi: 10.1093/annonc/mdt379 CrossRefGoogle Scholar
  48. 48.
    Hayes DN, Lucas AS, Tanvetyanon T, Krzyzanowska MK, Chung CH, Murphy BA, Gilbert J, Mehra R, Moore DT, Sheikh A, Hoskins J, Hayward MC, Zhao N, O’Connor W, Weck KE, Cohen RB, Cohen EE (2012) Phase II efficacy and pharmacogenomic study of Selumetinib (AZD6244; ARRY-142886) in iodine-131 refractory papillary thyroid carcinoma with or without follicular elements. Clin Cancer Res Off J Am Assoc Cancer Res 18(7):2056–2065. doi: 10.1158/1078-0432.CCR-11-0563 CrossRefGoogle Scholar
  49. 49.
    Brose MS, Nutting CM, Jarzab B, Elisei R, Siena S, Bastholt L, de la Fouchardiere C, Pacini F, Paschke R, Shong YK, Sherman SI, Smit JW, Chung J, Kappeler C, Pena C, Molnar I, Schlumberger MJ, on behalf of the Di (2014) Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet. doi: 10.1016/S0140-6736(14)60421-9 PubMedCentralGoogle Scholar
  50. 50.
    Brose MS, Jarzab B, Elisei R, Siena S, Bastholt L, De La Fouchardiere C, Pacini F, Paschke R, Nutting C, Shong YK, Sherman SI, Smit JW, Chung JW, Kappeler C, Molnar I, Schlumberger M (2014) Updated overall survival analysis of patients with locally advanced or metastatic radioactive iodine-refractory differentiated thyroid cancer (RAI-rDTC) treated with sorafenib on the phase 3 DECISION trial. ASCO Meet Abstr 32(15_suppl):6060Google Scholar
  51. 51.
    Brose MS, Nutting C, Jarzab B, Elisei R, Siena S, Bastholt L, de la Fouchardiere C, Pacini F, Paschke R, Shong YK, Sherman SI, Smit JW, Chung JW, Siedentop H, Molnar I, Schlumberger M (2013) Sorafenib in locally advanced or metastatic patients with radioactive iodine-refractory differentiated thyroid cancer: the phase III DECISION trial. ASCO Meet Abstr 31(18_suppl):4Google Scholar
  52. 52.
    Schlumberger M, Tahara M, Wirth LJ, Robinson B, Brose MS, Elisei R, Dutcus CE, de las Heras B, Zhu J, Habra MA, Newbold K, Shah MH, Hoff AO, Gianoukakis AG, Kiyota N, Taylor MH, Kim S-B, Krzyzanowska MK, Sherman SI (2014) A phase 3, multicenter, double-blind, placebo-controlled trial of lenvatinib (E7080) in patients with 131I-refractory differentiated thyroid cancer (SELECT). ASCO Meet Abstr 32(18_suppl):LBA6008Google Scholar
  53. 53.
    Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H, Chen C, Zhang X, Vincent P, McHugh M, Cao Y, Shujath J, Gawlak S, Eveleigh D, Rowley B, Liu L, Adnane L, Lynch M, Auclair D, Taylor I, Gedrich R, Voznesensky A, Riedl B, Post LE, Bollag G, Trail PA (2004) BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 64(19):7099–7109CrossRefPubMedGoogle Scholar
  54. 54.
    Dubauskas Z, Kunishige J, Prieto VG, Jonasch E, Hwu P, Tannir NM (2009) Cutaneous squamous cell carcinoma and inflammation of actinic keratoses associated with sorafenib. Clin Genitourin Cancer 7(1):20–23. doi: 10.3816/CGC.2009.n.003 CrossRefPubMedGoogle Scholar
  55. 55.
    Brose MS, Troxel AB, Redlinger M, Harlacker K, Redlinger C, Chalian AA, Flaherty KT, Loevner LA, Mandel SJ, O’Dwyer PJ (2009) Effect of BRAFV600E on response to sorafenib in advanced thyroid cancer patients. ASCO Meet Abstr 27(15S):6002Google Scholar
  56. 56.
    Okamoto K, Kodama K, Takase K, Sugi NH, Yamamoto Y, Iwata M, Tsuruoka A (2013) Antitumor activities of the targeted multi-tyrosine kinase inhibitor lenvatinib (E7080) against RET gene fusion-driven tumor models. Cancer Lett 340(1):97–103. doi: 10.1016/j.canlet.2013.07.007 CrossRefPubMedGoogle Scholar
  57. 57.
    Kim DW, Jo YS, Jung HS, Chung HK, Song JH, Park KC, Park SH, Hwang JH, Rha SY, Kweon GR, Lee SJ, Jo KW, Shong M (2006) An orally administered multitarget tyrosine kinase inhibitor, SU11248, is a novel potent inhibitor of thyroid oncogenic RET/papillary thyroid cancer kinases. J Clin Endocrinol Metab 91(10):4070–4076. doi: 10.1210/jc.2005-2845 CrossRefPubMedGoogle Scholar
  58. 58.
    Capdevila J, Trigo Perez JM, Aller J, Manzano JL, Garcia Adrian S, Zafon C, Reig O, Bohn U, Cillan E, Duran M, Gonzalez Astorga B, Lopez A, Javier M, Porras I, Reina JJ, Palacios N, Grande E, Grau JJ (2014) Axitinib treatment in advanced RAI-resistant differentiated thyroid cancer (DTC) and refractory medullary thyroid cancer (MTC). ASCO Meet Abstr 32(15_suppl):6027Google Scholar
  59. 59.
    Carlomagno F, Vitagliano D, Guida T, Ciardiello F, Tortora G, Vecchio G, Ryan AJ, Fontanini G, Fusco A, Santoro M (2002) ZD6474, an orally available inhibitor of KDR tyrosine kinase activity, efficiently blocks oncogenic RET kinases. Cancer Res 62(24):7284–7290PubMedGoogle Scholar
  60. 60.
    Harvey RD, Kauh JS, Ramalingam SS, Lewis CM, Chen Z, Lonial S, Blount IC, Shin DM, Khuri FR, Owonikoko TK (2010) Combination therapy with sunitinib and bortezomib in adult patients with radioiodine refractory thyroid cancer. ASCO Meet Abstr 28(15_suppl):5589Google Scholar
  61. 61.
    Harvey RD, Owonikoko TK, Lewis CM, Akintayo A, Chen Z, Tighiouart M, Ramalingam SS, Fanucchi MP, Nadella P, Rogatko A, Shin DM, El-Rayes B, Khuri FR, Kauh JS (2013) A phase 1 Bayesian dose selection study of bortezomib and sunitinib in patients with refractory solid tumor malignancies. Br J Cancer 108(4):762–765. doi: 10.1038/bjc.2012.604 PubMedCentralCrossRefPubMedGoogle Scholar
  62. 62.
    Ho AL, Grewal RK, Leboeuf R, Sherman EJ, Pfister DG, Deandreis D, Pentlow KS, Zanzonico PB, Haque S, Gavane S, Ghossein RA, Ricarte-Filho JC, Dominguez JM, Shen R, Tuttle RM, Larson SM, Fagin JA (2013) Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer. N Engl J Med 368(7):623–632. doi: 10.1056/NEJMoa1209288 PubMedCentralCrossRefPubMedGoogle Scholar
  63. 63.
    Wells SA Jr, Gosnell JE, Gagel RF, Moley J, Pfister D, Sosa JA, Skinner M, Krebs A, Vasselli J, Schlumberger M (2010) Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer. J Clin Oncol Off J Am Soc Clin Oncol 28(5):767–772. doi: 10.1200/JCO.2009.23.6604 CrossRefGoogle Scholar
  64. 64.
    Robinson BG, Paz-Ares L, Krebs A, Vasselli J, Haddad R (2010) Vandetanib (100 mg) in patients with locally advanced or metastatic hereditary medullary thyroid cancer. J Clin Endocrinol Metab 95(6):2664–2671. doi: 10.1210/jc.2009-2461 PubMedCentralCrossRefPubMedGoogle Scholar
  65. 65.
    Kurzrock R, Sherman SI, Ball DW, Forastiere AA, Cohen RB, Mehra R, Pfister DG, Cohen EE, Janisch L, Nauling F, Hong DS, Ng CS, Ye L, Gagel RF, Frye J, Muller T, Ratain MJ, Salgia R (2011) Activity of XL184 (Cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer. J Clin Oncol Off J Am Soc Clin Oncol 29(19):2660–2666. doi: 10.1200/JCO.2010.32.4145 CrossRefGoogle Scholar
  66. 66.
    Lam ET, Ringel MD, Kloos RT, Prior TW, Knopp MV, Liang J, Sammet S, Hall NC, Wakely PE Jr, Vasko VV, Saji M, Snyder PJ, Wei L, Arbogast D, Collamore M, Wright JJ, Moley JF, Villalona-Calero MA, Shah MH (2010) Phase II clinical trial of sorafenib in metastatic medullary thyroid cancer. J Clin Oncol Off J Am Soc Clin Oncol 28(14):2323–2330. doi: 10.1200/JCO.2009.25.0068 CrossRefGoogle Scholar
  67. 67.
    Schlumberger MJ, Elisei R, Bastholt L, Wirth LJ, Martins RG, Locati LD, Jarzab B, Pacini F, Daumerie C, Droz JP, Eschenberg MJ, Sun YN, Juan T, Stepan DE, Sherman SI (2009) Phase II study of safety and efficacy of motesanib in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer. J Clin Oncol Off J Am Soc Clin Oncol 27(23):3794–3801. doi: 10.1200/JCO.2008.18.7815 CrossRefGoogle Scholar
  68. 68.
    De Souza JA, Busaidy N, Zimrin A, Seiwert TY, Villaflor VM, Poluru KB, Reddy PL, Nam J, Vokes EE, Cohen EE (2010) Phase II trial of sunitinib in medullary thyroid cancer (MTC). ASCO Meet Abstr 28(15_suppl):5504Google Scholar
  69. 69.
    Wells SA Jr, Robinson BG, Gagel RF, Dralle H, Fagin JA, Santoro M, Baudin E, Elisei R, Jarzab B, Vasselli JR, Read J, Langmuir P, Ryan AJ, Schlumberger MJ (2012) Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol Off J Am Soc Clin Oncol 30(2):134–141. doi: 10.1200/JCO.2011.35.5040 CrossRefGoogle Scholar
  70. 70.
    Elisei R, Schlumberger MJ, Muller SP, Schoffski P, Brose MS, Shah MH, Licitra L, Jarzab B, Medvedev V, Kreissl MC, Niederle B, Cohen EE, Wirth LJ, Ali H, Hessel C, Yaron Y, Ball D, Nelkin B, Sherman SI (2013) Cabozantinib in progressive medullary thyroid cancer. J Clin Oncol Off J Am Soc Clin Oncol 31(29):3639–3646. doi: 10.1200/JCO.2012.48.4659 CrossRefGoogle Scholar
  71. 71.
    Wedge SR, Ogilvie DJ, Dukes M, Kendrew J, Chester R, Jackson JA, Boffey SJ, Valentine PJ, Curwen JO, Musgrove HL, Graham GA, Hughes GD, Thomas AP, Stokes ES, Curry B, Richmond GH, Wadsworth PF, Bigley AL, Hennequin LF (2002) ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration. Cancer Res 62(16):4645–4655PubMedGoogle Scholar
  72. 72.
    Ha HT, Lee JS, Urba S, Koenig RJ, Sisson J, Giordano T, Worden FP (2010) A phase II study of imatinib in patients with advanced anaplastic thyroid cancer. Thyroid Off J Am Thyroid Assoc 20(9):975–980. doi: 10.1089/thy.2010.0057 CrossRefGoogle Scholar
  73. 73.
    Podtcheko A, Ohtsuru A, Namba H, Saenko V, Starenki D, Palona I, Sedliarou I, Rogounovitch T, Yamashita S (2006) Inhibition of ABL tyrosine kinase potentiates radiation-induced terminal growth arrest in anaplastic thyroid cancer cells. Radiat Res 165(1):35–42CrossRefPubMedGoogle Scholar
  74. 74.
    Capdevila J, Iglesias L, Halperin I, Segura A, Martinez-Trufero J, Vaz MA, Corral J, Obiols G, Grande E, Grau JJ, Tabernero J (2012) Sorafenib in metastatic thyroid cancer. Endocr Relat Cancer 19(2):209–216. doi: 10.1530/ERC-11-0351 CrossRefPubMedGoogle Scholar
  75. 75.
    Savvides P, Nagaiah G, Lavertu P, Fu P, Wright JJ, Chapman R, Wasman J, Dowlati A, Remick SC (2013) Phase II trial of sorafenib in patients with advanced anaplastic carcinoma of the thyroid. Thyroid Off J Am Thyroid Assoc 23(5):600–604. doi: 10.1089/thy.2012.0103 CrossRefGoogle Scholar
  76. 76.
    Bible KC, Suman VJ, Menefee ME, Smallridge RC, Molina JR, Maples WJ, Karlin NJ, Traynor AM, Kumar P, Goh BC, Lim WT, Bossou AR, Isham CR, Webster KP, Kukla AK, Bieber C, Burton JK, Harris P, Erlichman C, Mayo Phase C, Mayo Clinic Endocrine Malignances Disease Oriented G (2012) A multiinstitutional phase 2 trial of pazopanib monotherapy in advanced anaplastic thyroid cancer. J Clin Endocrinol Metab 97(9):3179–3184. doi: 10.1210/jc.2012-1520 PubMedCentralCrossRefPubMedGoogle Scholar
  77. 77.
    Sosa JA, Elisei R, Jarzab B, Balkissoon J, Lu SP, Bal C, Marur S, Gramza A, Yosef RB, Gitlitz B, Haugen BR, Ondrey F, Lu C, Karandikar SM, Khuri F, Licitra L, Remick SC (2014) Randomized safety and efficacy study of fosbretabulin with paclitaxel/carboplatin against anaplastic thyroid carcinoma. Thyroid Off J Am Thyroid Assoc 24(2):232–240. doi: 10.1089/thy.2013.0078 CrossRefGoogle Scholar
  78. 78.
    Gramza AW, Balasubramaniam S, Fojo AT, Ward J, Wells SA (2013) Phase I/II trial of crolibulin and cisplatin in solid tumors with a focus on anaplastic thyroid cancer: phase I results. ASCO Meet Abstr 31(15_suppl):6074Google Scholar
  79. 79.
    Wunderlich A, Khoruzhyk M, Roth S, Ramaswamy A, Greene BH, Doll D, Bartsch DK, Hoffmann S (2013) Pretherapeutic drug evaluation by tumor xenografting in anaplastic thyroid cancer. J Surg Res 185(2):676–683. doi: 10.1016/j.jss.2013.06.017 CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland (outside the USA) 2015

Authors and Affiliations

  1. 1.Department of Internal MedicineUniversity of Nebraska Medical CenterOmahaUSA
  2. 2.Division of Hematology/Oncology, Department of Internal MedicineVA Nebraska-Western Iowa Health Care SystemOmahaUSA
  3. 3.Division of Oncology-Hematology, Department of Internal MedicineUniversity of Nebraska Medical CenterOmahaUSA

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