Skip to main content

Advertisement

SpringerLink
Log in

Activity and safety of sunitinib in patients with advanced radioactive iodine-refractory differentiated thyroid carcinoma in clinical practice

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Our aim was to evaluate the effectiveness of off-label use of sunitinib in patients with advanced differentiated thyroid carcinoma (DTC) refractory to radioactive iodine (RAI) therapy. We performed a retrospective analysis of patients treated in the setting of clinical practice in a University General Hospital. Eleven consecutive patients (5 women, 6 men, mean age 63.0 ± 12.9 year) with advanced papillary (n = 7) or follicular (n = 4) thyroid carcinoma not suitable for curative surgery or RAI therapy were studied. Two patients were treated with one line of tyrosine kinase inhibitors before sunitinib therapy. All patients had evidence of objective progressive disease (PD). We analysed the objective response rate (ORR) and changes in thyroglobulin levels during therapy. Complete response was achieved in 1 patient (9 %) and partial response (PR) in 2 patients (18 %). Five patients (45 %) had stable disease (SD). Therefore, ORR was 27 % and disease control rate was 72 %. We found that the decrement in thyroglobulin concentrations was significantly higher in patients with radiological disease control than in patients with PD. Most frequent grade 1 and 2 adverse events were fatigue, mucositis, hand-and-foot syndrome, hyporexia, rash, hypertension, and edema. In routine clinical practice, sunitinib appears to be effective and feasible in patients with advanced RAI-refractory DTC. Most patients achieved SD or PR, despite having PD at the start of treatment, and safety profile was consistent with that reported in previous clinical trials.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. E. Grande, J.J. Díez, C. Zafón, C. Capdevila, Thyroid cancer: molecular aspects and new therapeutic strategies. J. Thyroid Res. (2012). doi:10.1155/2012/847108

    PubMed Central  PubMed  Google Scholar 

  2. C. Durante, N. Haddy, E. Baudin, S. Leboulleux, D. Hartl, J.P. Travagli, B. Caillou, M. Ricard, J.D. Lumbroso, F. DeVathaire, M. Schlumberger, Long term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. J. Clin. Endocrinol. Metab. 91, 2892–2899 (2006)

    Article  CAS  PubMed  Google Scholar 

  3. E. Baudin, M. Schlumberger, New therapeutic approaches for metastatic thyroid carcinoma. Lancet Oncol. 8, 148–156 (2007)

    Article  CAS  PubMed  Google Scholar 

  4. F. Pacini, M. Schlumberger, H. Dralle, R. Elisei, J.W.A. Smit, W. Wiersinga, European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium. Eur. J. Endocrinol. 154, 787–803 (2006)

    Article  CAS  PubMed  Google Scholar 

  5. X.M. Yu, C.Y. Lo, W.F. Chan, K.Y. Lam, P. Leung, J.M. Luk, Increased expression of vascular endothelial growth factor C in papillary thyroid carcinoma correlates with cervical lymph node metastases. Clin. Cancer Res. 11, 8063–8069 (2005)

    Article  CAS  PubMed  Google Scholar 

  6. M. Xing, B.R. Haugen, M. Schlumberger, Progress in molecular-based management of differentiated thyroid cancer. Lancet 381(9871), 1058–1069 (2013)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. V. Gupta-Abramson, A.B. Troxel, A. Nellore, K. Puttaswamy, M. Redlinger, K. Ransone, S.J. Mandel, K.T. Flaherty, L.A. Loevner, P.J. O’Dwyer, M.S. Brose, Phase II trial of sorafenib in advanced thyroid cancer. J. Clin. Oncol. 26, 4714–4719 (2008)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. R.T. Kloos, M.D. Ringel, M.V. Knopp, N.C. Hall, M. King, R. Stevens, J. Liang, P.E. Wakely Jr, V.V. Vasko, M. Saji, J. Rittenberry, L. Wei, D. Arbogast, M. Collamore, J.J. Wright, M. Grever, M.H. Shah, Phase II trial of sorafenib in metastatic thyroid cancer. J. Clin. Oncol. 27, 1675–1684 (2009)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. M.H. Massicotte, M. Brassard, M. Claude-Desroches, I. Borget, F. Bonichon, A.L. Giraudet, C. Do Cao, C.N. Cougnet, S. Leboulleux, E. Baudin, M. Schlumberger, C. de la Fouchardière, Tyrosine kinase inhibitor treatment in patients with metastatic thyroid carcinomas: a retrospective study of the TUTHYREF network. Eur. J. Endocrinol. 170, 575–582 (2014)

    Article  CAS  PubMed  Google Scholar 

  10. 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 JWA, Chung J, Kappeler C, Peña C, Molnár I, Schlumberger M, DECISION investigators, Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomized, double-blind, phase 3 trial. Lancet (2014). doi:10.1016/S0140-6736(14)60421-9

  11. L.Q.M. Chow, S. Eckhardt, Sunitinib: from rational design to clinical efficacy. J. Clin. Oncol. 25, 884–896 (2007)

    Article  CAS  PubMed  Google Scholar 

  12. Cohen EE, Needles BM, Cullen KJ, Wong SJ, Wade JL, Ivy SP, Villaflor VM, Seiwert TY, Nichols K, voker EE, Phase 2 study of sunitinib in refractory thyroid cancer. J. Clin. Oncol. 26 suppl: 6025 (abstract) (2008)

  13. Ravaud A, de la Fouchardiere C, Courbon F, Asselineau J, Klein M, Nicoli-Sire P, Bournaud C, Delord J, Weryha G, Catargi B, Sunitinib in patients with refractory advanced thyroid cancer: the THYSU phase II trial. J. Clin. Oncol. 26, 6058 (abstract) (2008)

  14. A. Ravaud, C. de la Fouchardière, J. Asselineau, J.P. Delord, C. Do Cao, P. Niccoli, P. Rodien, M. Klein, B. Catargi, Efficacy of sunitinib in advanced medullary thyroid carcinoma: intermediate results of phase II THYSU. Oncologist 15, 212–213 (2010)

    Article  PubMed Central  PubMed  Google Scholar 

  15. L.L. Carr, D.A. Mankoff, B.H. Goulart, K.D. Eaton, P.T. Capell, E.M. Kell, J.E. Bauman, R.G. Martins, 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. 16, 5260–5268 (2010)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Sherman SI, Tuttle RM, Ball DW, Byrd D, Clark OH, Daniels GH, Dilawari RA, Doherty GM, Ehya H, Farrar WB, Haddad RI, Kandeel F, Kloos RT, Kopp P, Lamonica DM, Loree TR, Lydiatt WM, McCaffrey J, Olson JA, Parks L, Ridge JA, Shah JP, Sturgeon C, Waguespack SG, Wang TN, Wirth LJ, 2009 NCCN practice guidelines in oncology: thyroid carcinoma. J. Natl. Compr. Canc. Netw. 1.2009 (2009)

  17. M. Schlumberger, S.I. Sherman, Approach to the patient with advanced differentiated thyroid cancer. Eur. J. Endocrinol. 166, 5–11 (2009)

    Article  Google Scholar 

  18. E.A. Eisenhauer, P. Therasse, J. Bogaerts, L.H. Schwartz, D. Sargent, R. Ford, J. Dancey, S. Arbuck, S. Gwyther, M. Mooney, L. Rubinstein, L. Shankar, L. Dodd, R. Kaplan, D. Lacombe, J. Verweij, New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur. J. Cancer 45, 228–247 (2009)

    Article  CAS  PubMed  Google Scholar 

  19. Cancer Therapy Evaluation Program, Common Terminology Criteria for Adverse Events, Version 3.0, DCTD, NCI, NIH, DHHS. March 31, 2003. Publish Date: August 9, 2006. http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf

  20. T.C. Schneider, R.M. Abdulrahman, E.P. Corssmit, H. Morreau, J.W.A. Smit, E. Kapiteijn, 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. 167, 643–650 (2012)

    Article  CAS  PubMed  Google Scholar 

  21. K.C. Bible, V.J. Suman, J.R. Molina, R.C. Smallridge, W.J. Maples, M.E. Menefee, J. Rubin, K. Sideras, J.C. Morris III, B. McIver, J.K. Burton, K.P. Webster, C. Bieber, A.M. Traynor, P.J. Flynn, B.C. Goh, H. Tang, S.P. Ivy, C. Erlichman, Endocrine Malignancies Disease Oriented Group, Mayo Clinic Cancer Center, Mayo Phase 2 Consortium, Efficacy of pazopanib in progressive, radioiodine-refractory, metastatic differentiated thyroid cancers: results of a phase 2 consortium study. Lancet Oncol. 11, 962–972 (2010)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. S.I. Sherman, B. Jarzab, M.E. Cabanillas, L.F. Licitra, F. Pacini, R. Martins, B. Robinson, D. Ball, J. McCaffrey, M.H. Shah, A phase II trial of the multi-targeted kinase inhibitor, lenvatinib (E7080), in advanced radioiodine (RAI)-refractory differentiated thyroid cancer (DTC). ASCO Meeting Abstracts, 29, abstract 5503 (2011)

  23. M.E. Cabanillas, S.G. Waguespack, Y. Bronstein, M.D. Williams, L. Feng, M. Hernandez, A. Lopez, S.I. Shrman, N.L. Busaidy, Treatment with tyrosine kinase inhibitors for patients with differentiated thyroid carcinoma: the M.D. Anderson experience. J. Clin. Endocrinol. Metab. 95, 2588–2595 (2010)

    Article  CAS  PubMed  Google Scholar 

  24. J. Capdevila, L. Iglesias, I. Halperín, A. Segura, J. Martínez-Trufero, M.A. Vaz, J. Corral, G. Obiols, E. Grande, J.J. Grau, J. Tabernero, Sorafenib in metastatic thyroid cancer. Endocr. Relat. Cancer 19, 209–216 (2012)

    Article  CAS  PubMed  Google Scholar 

  25. V. Marotta, V. Ramundo, L. Camera, M. Del Prete, R. Fonti, R. Esposito, G. Palmieri, M. Salvatore, M. Vitale, A. Colao, A. Faggiano, Sorafenib in advanced iodine-refractory differentiated thyroid cancer: efficacy, safety and exploratory analysis of role of serum thyroglobulin and FDG-PET. Clin. Endocrinol. 78, 760–767 (2013)

    Article  CAS  Google Scholar 

  26. G. Sonpavde, T.K. Choueiri, B. Escudier, V. Ficarra, T.E. Hutson, P.F. Mulders, J.J. Patard, B.I. Rini, M. Staehler, C.N. Sternberg, C.G. Stief, Sequencing of agents for metastatic renal cell carcinoma: can we customize therapy? Eur. Urol. 61, 307–316 (2012)

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

The authors have no conflict of interest in relation to this article.

Author information

Authors and Affiliations

  1. Department of Endocrinology, Hospital Universitario Ramón y Cajal, Madrid, Spain

    Juan J. Díez & Pedro Iglesias

  2. Universidad de Alcalá de Henares, Madrid, Spain

    Juan J. Díez

  3. Department of Medical Oncology, Hospital Universitario Ramón y Cajal, Madrid, Spain

    Teresa Alonso & Enrique Grande

Authors
  1. Juan J. Díez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pedro Iglesias
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Teresa Alonso
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Enrique Grande
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Juan J. Díez.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Díez, J.J., Iglesias, P., Alonso, T. et al. Activity and safety of sunitinib in patients with advanced radioactive iodine-refractory differentiated thyroid carcinoma in clinical practice. Endocrine 48, 582–588 (2015). https://doi.org/10.1007/s12020-014-0356-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-014-0356-1

Keywords

Search

Navigation