The majority of deaths due to thyroid cancer occur in patients with advanced DTC refractory to radioactive iodine. The spectacular advances in molecular medicine of recent years have opened new therapeutic possibilities. Currently, there is general agreement that treatment with Tyrosine Kinase Inhibitors (TKI) should only be considered in patients with differentiated thyroid carcinoma refractory to radioactive iodine, with progressive and / or symptomatic metastatic disease that can not otherwise be treated locally. Most of these "new molecules" are multichannel inhibitors with varied action, which interact on different proteins such as RET, BRAF, cKIT, MET, EGFR, MAPK, PDGFR, etc. In addition, they have the additional advantage that they markedly prevent angiogenesis by acting on VEGFR 1, 2, and 3. TKI are associated with progression-free survival but not curative. Also, causes adverse effects that can affect the quality of life.The prolongation of progression-free survival has been demonstrated with sorafenib and lenvatinib compared with placebo in two phase III trials. These two drugs have been approved by the FDA and the European Medicines Agency for use in patients refractory to radioactive iodine with metastatic disease. Based on the Phase II Trials there are other Tyrosine Kinase Inhibitors (TKI) available such as sunitinib, axitinib or pazopanib that can produce some kind of clinical benefit and therefore need further investigation.
Lynda Marianela Vásconez Proaño,
New Targets in Advanced Thyroid Cancer Refractory Iodine, Cancer Research Journal.
Vol. 7, No. 2,
2019, pp. 39-44.
Eizaguirrea Garcilaso Riesco, Galofré Juan Carlos, Grande Enrique et al., Spanish Consensus for the management of patients with advanced radioactive iodine refractory differentiated thyroid cancer, Endocrinología y Nutrición, Elsevier 2016; 63 (4):e17- e24.
Galofré Juan Carlos, Gómez-Sáez José Manuel, Alvarez Escola Cristina et al., Uso de nuevas moléculas en el tratamiento del cáncer avanzado de tiroides, Endocrinología y Nutrición, Elsevier Doyma 2011; 58 (8):381- 386, doi:10.1016/j.endonu.2011.07.001.
Cabanillas Maria E, Amir Habra Mouhammed, Anti-tumour treatment, Lenvatinib : Role in thyroid cancer and other solid tumors, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, Cancer Treatment Reviews, Elsevier, 42 (2016) 47-55, doi.org/10.1016/j.ctrv.2015.11.003.
Nair Abhilasha, Lemery Steven J., Yang Jun et al., FDA Approval Summary: Lenvatinib for Progressive, Radio-iodine–Refractory Differentiated Thyroid Cancer, Clinical Cancer Research, American Association for Cancer Research, 21 (23) December 1, 2015, doi: 10.1158/1078-0432.CCR-15-1377.
Schlumberger Martin, Barbara Jarzab Barbara, Cabanillas Maria E et al., A Phase II Trial of the Multitargeted Tyrosine Kinase Inhibitor Lenvatinib (E7080) in Advanced Medullary Thyroid Cancer, Clinical Cancer Research, 22 (1) Aug 26, 2015, page 44-53, doi: 10.1158/1078-0432. CCR-15-1127.
Thornton Katherine, Kim Geoffrey, Maher V. Ellen et al., Vandetanib for the Treatment of Symptomatic or Progressive Medullary Thyroid Cancer in Patients with Unresectable Locally Advanced or Metastatic Disease: U.S. Food and Drug Administration Drug Approval Summary, CCR Perspectives in Drug Approval, American Association for Cancer Research, Clin Cancer Res; 18 (14) Jun 4, 2012, pages 3722-30 doi: 10.1158/1078-0432.CCR-12-0411.
Fallahi Poupak, Di Bari Flavia, Ferrari Silvia Martina et al., Selective use of vandetanib in the treatment of thyroid cancer, Drug Design, Development and Therapy, 2015:9 3459–3470, doi.org/10.2147/DDDT.S72495.
Haddad Robert I., Dana - Farber Cancer Institute, Harvard Medical School; and Brigham and Women’s Hospital, Boston, MA, How to Incorporate New Tyrosine Kinase Inhibitors in the Treatment of Patients With Medullary Thyroid Cancer, Journal of Clinical Oncology, Volume 31 Number 29 October 10 2013: pp 3618-3620, doi: 10.1200/JCO.2013.51.5098.
Cohen Ezra E. W., Rosen Lee S., Vokes Everett E. et al., Axitinib Is an Active Treatment for All Histologic Subtypes of Advanced Thyroid Cancer: Results From a Phase II Study, American Society of Clinical Oncology, J Clin Oncol 26:4708-4713, Volume 26, Number 29, October 10 2008, doi: 10.1200/JCO.2007.15.9566.
Abramson Vandana Gupta, Troxel Andrea B., Nellore Anoma et al., Phase II Trial of Sorafenib in Advanced Thyroid Cancer, American Society of Clinical Oncology, Volume 26 Number 29 October 10 2008, J Clin Oncol 26:4714-4719, doi: 10.1200/JCO.2008.16.3279.
Brose Marcia S, Nutting Christopher M, Jarzab Barbara et al., Sorafenib in radioactive iodine-refractory, locally advanced or metastatic diﬀerentiated thyroid cancer: a randomised, double-blind, phase 3 trial, www.thelancet.com, Jul 26, 2014, 384 (9940): pages 319-28, doi.org/10.1016/S0140 6736 (14) 60421-9
Pacini F., Castagna M. G., Brilli L., Pentheroudakis G. et al, on behalf of the ESMO Guidelines Working Group, Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, clinical practical guidelines, Annals of Oncology, Volume 23, Issue suppl_7, 1 October 2012, Pages vii110–vii119, doi:10.1093/annonc/mds230.
Wells Jr Samuel A., Robinson Bruce G., Gagel Robert F.et al, Vandetanib in Patients With Locally Advanced or Metastatic Medullary Thyroid Cancer: A Randomized, Double-Blind Phase III Trial, American Society of Clinical Oncology, January 10,2012. 30 (2): pages 134-141, doi: 10.1200/JCO.2011.35.5040.
Haddad Robert I, MD Chair, Farber Dana, Brigham and Women Cancer Center, Lydiatt William M., MD Vice-Chair Fred, Pamela Buffett Cancer Center, Bischoff Lindsay, MD Vanderbilt-Ingram Cancer Center, Guias NCCN, 30 (2): page THYR-B, January 10 2012.
Corey J. Langer, MD, FACP, Tratamiento del cáncer de tiroides, Clinical Care Options, LLC, In Practice, 4/1/16, USF Health, chapter 4, page 12.
Brea Mayte, Navarro Ana, Avances en Cáncer de Tiroides, Sociedad Española de Oncología Médica, 2015, page 2.
Schmidt Angélica, Cross Graciela, Pitoia Fabián, Metástasis a distancia en cáncer diferenciado de tiroides: diagnóstico y tratamiento, Hospital de Clínicas «José de San Martín», División Endocrinología, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina, rev argent endocrinol metab. 2017; 54 (2):92–100, doi.org/10.1016/j.raem.2017.05.001 0326-4610.