Abstract
Targeted therapy in progressive metastatic medullary thyroid cancer (MTC) with current FDA-approved agents, vandetanib and cabozantinib, is associated with improved progression-free survival.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Elisei R, Schlumberger MJ, Muller SP, et al. Cabozantinib in progressive medullary thyroid cancer. J Clin Oncol. 2013;31:3639–46.
Wells SA Jr, Robinson BG, Gagel RF, et al. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol. 2012;30:134–41.
Orlandi F, Caraci P, Berruti A, et al. Chemotherapy with dacarbazine and 5-fluorouracil in advanced medullary thyroid cancer. Ann Oncol. 1994;5:763–5.
Food and Drug Administration. CDER clinical pharmacology and biopharmaceutics review[s] for cabozantinib [COMETRIQ], 2012.
Carlomagno F, Guida T, Anaganti S, et al. Disease associated mutations at valine 804 in the RET receptor tyrosine kinase confer resistance to selective kinase inhibitors. Oncogene. 2004;23:6056–63.
Mologni L, Redaelli S, Morandi A, et al. Ponatinib is a potent inhibitor of wild-type and drug-resistant gatekeeper mutant RET kinase. Mol Cell Endocrinol. 2013;377:1–6.
Cote GJ, Grubbs E, Hofmann MC. Thyroid C-cell biology and oncogenic transformation. In: Raue F, editor. Medullary thyroid carcinoma: Biology—Management—Treatment. Springer International Publishing; 2015 (in press).
Mian C, Pennelli G, Barollo S, et al. Combined RET and Ki-67 assessment in sporadic medullary thyroid carcinoma: a useful tool for patient risk stratification. Eur J Endocrinol. 2011;164:971–6.
Elisei R, Cosci B, Romei C, et al. Prognostic significance of somatic RET oncogene mutations in sporadic medullary thyroid cancer: a 10-year follow-up study. J Clin Endocrinol Metab. 2008;93:682–7.
Moura MM, Cavaco BM, Leite V. RAS proto-oncogene in medullary thyroid carcinoma. Endocr Relat Cancer. 2015;22:R235–52.
Hong DS, Cabanillas ME, Wheler J, et al. 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. 2011;96:997–1005.
Rapa I, Saggiorato E, Giachino D, et al. Mammalian target of rapamycin pathway activation is associated to RET mutation status in medullary thyroid carcinoma. J Clin Endocrinol Metab. 2011;96:2146–53.
Lyra J, Vinagre J, Batista R, et al. mTOR activation in medullary thyroid carcinoma with RAS mutation. Eur J Endocrinol. 2014;171:633–40.
Tamburrino A, Molinolo AA, Salerno P, et al. Activation of the mTOR pathway in primary medullary thyroid carcinoma and lymph node metastases. Clin Cancer Res. 2012;18:3532–40.
Manfredi GI, Dicitore A, Gaudenzi G, et al. PI3K/Akt/mTOR signaling in medullary thyroid cancer: a promising molecular target for cancer therapy. Endocrine. 2015;48:363–70.
Sherman E, Ho A, Fury M, et al. Combination of everolimus and sorafenib in the treatment of thyroid cancer: update on phase II study. J Clin Oncol. 2015;33.
van Veelen W, Klompmaker R, Gloerich M, et al. P18 is a tumor suppressor gene involved in human medullary thyroid carcinoma and pheochromocytoma development. Int J Cancer. 2009;124:339–45.
Bagheri-Yarmand R, Sinha KM, Gururaj AE, et al. A novel dual kinase function of the RET proto-oncogene negatively regulates activating transcription factor 4-mediated apoptosis. J Biol Chem. 2015;290:11749–61.
Dadu R, Rodriguez J, Wistuba I, et al. Immune markers in medullary thyroid cancer (MTC) and their clinical significance. Paper presented at the International Thyroid Congress, Orlando, FL, 2015.
Sherman SI. Lessons learned and questions unanswered from use of multitargeted kinase inhibitors in medullary thyroid cancer. Oral Oncol. 2013;49:707–10.
Hu MI, Ying AK, Jimenez C. Update on medullary thyroid cancer. Endocrinol Metab Clin North Am. 2014;43:423–42.
Capp C, Wajner SM, Siqueira DR, et al. Increased expression of vascular endothelial growth factor and its receptors, VEGFR-1 and VEGFR-2, in medullary thyroid carcinoma. Thyroid. 2010;20:863–71.
Rodriguez-Antona C, Pallares J, Montero-Conde C, et al. Overexpression and activation of EGFR and VEGFR2 in medullary thyroid carcinomas is related to metastasis. Endocr Relat Cancer. 2010;17:7–16.
Sherman SI, Cohen EE, Schoffski P, et al. Efficacy of cabozantinib (Cabo) in medullary thyroid cancer (MTC) patients with RAS or RET mutations: results from a phase III study. J Clin Oncol. 2013;31.
Schlumberger M, Elisei R, Muller SP, et al. Final overall survival analysis of EXAM, an international, double-blind, randomized, placebo-controlled phase III trial of cabozantinib (Cabo) in medullary thyroid carcinoma (MTC) patients with documented RECIST progression at baseline. J Clin Oncol. 2015;33.
De Falco V, Buonocore P, Muthu M, et al. Ponatinib (AP24534) is a novel potent inhibitor of oncogenic RET mutants associated with thyroid cancer. J Clin Endocrinol Metab. 2013;98:E811–9.
NCI: A Phase II Study of Ponatinib in Advanced or Metastatic Medullary Thyroid Cancer. In: clinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 (cited 28 Aug 2015). Available from: https://clinicaltrials.gov/ct2/show/study/NCT01838642?view=record. NLM identifier: NCT01838642.
Schlumberger M, Tahara M, Wirth LJ, et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med. 2015;372:621–30.
Takahashi S, Tahara M, Kiyota N, et al: Phase II study of lenvatinib (len), a multi-targeted tyrosine kinase inhibitor, in patients (pts) with all histologic subtypes of advanced thyroid cancer (differentiated, medullary, and anaplastic). Ann Oncol. 2014;25:iv340–56.
Schlumberger M, Jarzab B, Cabanillas ME, et al. A Phase 2 trial of the multi-targeted tyrosine kinase inhibitor lenvatinib (E7080) in advanced medullary thyroid cancer (MTC). Clin Cancer Res. 2015.
Carr LL, Mankoff DA, Goulart BH, et al. 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. 2010;16:5260–8.
De Souza JA, Busaidy N, Zimrin A, et al. Phase II trial of sunitinib in medullary thyroid cancer (MTC). J Clin Oncol. 2010;28:suppl;abstr 5504.
Richeldi L, du Bois RM, Raghu G, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2071–82.
Hilberg F, Roth GJ, Krssak M, et al. BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008;68:4774–82.
EORTC: Nintedanib(BIBF1120) in Thyroid Cancer, pp In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). 2000-(cited 28 Aug). Available from: https://clinicaltrials.gov/ct2/show/NCT01788982. NLM identifier: NCT01788982.
Bible KC, Suman VJ, Molina JR, et al. A multicenter phase 2 trial of pazopanib in metastatic and progressive medullary thyroid carcinoma: MC057H. J Clin Endocrinol Metab. 2014;99:1687–93.
Dadu R, Devine C, Hernandez M, et al. Role of salvage targeted therapy in differentiated thyroid cancer patients who failed first-line sorafenib. J Clin Endocrinol Metab. 2014;99:2086–94.
Weitzman SP, Peicher KT, Dadu R, et al. Salvage therapy: when a tyrosine kinase inhibitor (TKI) Fails in Advanced Medullary Thyroid Cancer (MTC). Endocr Rev. 2015;36:OR44-4.
Cleary JM, Sadow PM, Randolph GW, et al. Neoadjuvant treatment of unresectable medullary thyroid cancer with sunitinib. J Clin Oncol. 2010;28:e390–2.
Zaytseva YY, Valentino JD, Gulhati P, et al. mTOR inhibitors in cancer therapy. Cancer Lett. 2012;319:1–7.
Laplante M, Sabatini DM. mTOR signaling at a glance. J Cell Sci. 2009;122:3589–94.
Menon S, Manning BD. Common corruption of the mTOR signaling network in human tumors. Oncogene. 2008;27(Suppl 2):S43–51.
Lorch J, Busaidy N, Ruan D, et al. A phase II study of everolimus in patients with aggressive RAI refractory (RAIR) thyroid cancer (TC). J Clin Oncol. 2013;31.
Baksh K, Weber J. Immune checkpoint protein inhibition for cancer: preclinical justification for CTLA-4 and PD-1 blockade and new combinations. Semin Oncol. 2015;42:363–77.
Bilusic M, Heery CR, Arlen PM, et al. Phase I trial of a recombinant yeast-CEA vaccine (GI-6207) in adults with metastatic CEA-expressing carcinoma. Cancer Immunol Immunother. 2014;63:225–34.
Rowinsky EK, Windle JJ, Von Hoff DD. Ras protein farnesyltransferase: a strategic target for anticancer therapeutic development. J Clin Oncol. 1999;17:3631–52.
Lam ET, Ringel MD, Kloos RT, et al. Phase II clinical trial of sorafenib in metastatic medullary thyroid cancer. J Clin Oncol. 2010;28:2323–30.
Oncology K. An open label phase II study of tipifarnib in advanced non-hematological malignancies with HRAS mutations. In: clinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-(cited 31 Aug 2015). Available from: https://clinicaltrials.gov/ct2/show/record/NCT02383927. NLM identifier: NCT02383927.
Brem GJ, Mylonas I, Bruning A. Eeyarestatin causes cervical cancer cell sensitization to bortezomib treatment by augmenting ER stress and CHOP expression. Gynecol Oncol. 2013;128:383–90.
Vidula N, Rugo HS. Cyclin-Dependent Kinase 4/6 Inhibitors for the Treatment of Breast Cancer: A Review of Preclinical and Clinical Data. Clin Breast Cancer. 2015.
Desai AV, El-Bakkar H, Abdul-Hay M. Novel agents in the treatment of chronic lymphocytic leukemia: a review about the future. Clin Lymphoma Myeloma Leuk. 2015;15:314–22.
Dadu R, Hu MI, Cleeland CS, et al. The efficacy of the natural clay, Calcium Aluminosilicate Anti-Diarrheal (CASAD), in reducing medullary thyroid cancer-related diarrhea and its effects on quality of life: a pilot study. Thyroid 2015.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Zwiener, J.E., Kwatampora, L.J., Busaidy, N.L. (2016). Emerging Therapies for Progressive Metastatic Medullary Thyroid Cancer. In: Wang, T., Evans, D. (eds) Medullary Thyroid Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-39412-1_17
Download citation
DOI: https://doi.org/10.1007/978-3-319-39412-1_17
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-39410-7
Online ISBN: 978-3-319-39412-1
eBook Packages: MedicineMedicine (R0)