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Onkologische Welt 2015; 06(06): 255-259
DOI: 10.1055/s-0037-1608741
Innovation Schilddrüse
Schattauer GmbH

Systemische Behandlung des fortgeschrittenen differenzierten und medullären Schilddrüsenkarzinoms

Systemic treatment of advanced differentiated and medullary thyroid cancerOverview and practical aspects
M.C. Kreissl
1   Department of Nuclear Medicine, Central Hospital of Augsburg, Germany
2   Department of Nuclear Medicine, University Hospital, University of Wuerzburg, Germany
,
M. Fassnacht
3   Division of Endocrinology, Dept. of Internal Medicine I, University Hospital, University of Wuerzburg, Germany
,
S.P. Mueller
4   Department of Nuclear Medicine, University Hospital of Essen, Germany
› Institutsangaben
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Publikationsverlauf

Publikationsdatum:
16. November 2017 (online)

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Zusammenfassung

In den vergangenen Jahren wurden drei neue Substanzen für die molekular gezielte Therapie des fortgeschrittenen und progredienten Schilddrüsenkarzinoms zugelassen: Vandetanib und Cabozantinib für das medulläre Schilddrüsenkarzinom sowie Sorafenib für das Radioiod-refraktäre differenzierte Schilddrüsenkarzinom. Die Selektion der Patienten durch ein interdisziplinäres Team sowie die Aufklärung der Patienten spielt eine wesentliche Rolle, wenn diese Behandlung in Betracht gezogen bzw. begonnen wird. Nur Patienten mit hoher Tumorlast und/oder symptomatischer bzw. progredienter Erkrankung, die lokalen Therapien nicht zugänglich ist, sollten behandelt werden. Um eine gute Lebensqualität zu erhalten, ist das Management der unerwünschten Arzneimittelwirkungen von größter Bedeutung. Aufgrund der Wirkweise der Tyrosinkinasehemmer ist der Verlauf der Tumormarker Calcitonin und Thyreoglobulin nur bedingt zur Beurteilung des Therapieansprechens und zum Follow-up geeignet, deshalb kommt der morphologischen und metabolischen Bildgebung besondere Bedeutung zu. Ein umschriebener oder geringer Progress sollte nicht unbedingt die Beendigung der Behandlung oder eine Therapieumstellung nach sich ziehen. In der nahen Zukunft werden weitere Substanzen verfügbar sein.

Nachdruck aus und zu zitieren als: Nuklearmedizin 2015; 54: 88–93

Summary

In the last few years, three new drugs for targeted systemic therapies have been approved for advanced and progressive thyroid cancer, namely vandetanib and cabozantinib for medullary and sorafenib for radioiodine refractory differentiated thyroid cancer. Patient selection by an interdisciplinary team and education of patients by the treating physicians play a major role when such a treatment is considered and initiated. Only patients with significant tumor burden and/or symptomatic disease or progression, which cannot be controlled by local therapies, should be treated. In order to preserve quality of life, the management of adverse effects is of utmost importance. Due to the mechanism of action of these tyrosine kinase inhibitors, the reliability of serum tumour markers, calcitonin and thyroglobulin, is limited for the assessment of response and follow-up, therefore morphological and metabolic imaging is of great importance. Minor or localized progression should not automatically trigger the termination of treatment or change of drug. In the near future, it is expected that additional drugs become available.

Schlüsselwörter

Medulläres Schilddrüsenkarzinom - differenziertes Schilddrüsenkarzinom - systemische Therapie - Tyrosinkinasehemmer

Keywords

Medullary thyroid carcinoma - differentiated thyroid cancer - systemic therapy - tyrosine kinase inhibitor
 

  • References

  • 1 Verburg FA, Mader U, Tanase K. et al. Life expectancy is reduced in differentiated thyroid cancer patients >/= 45 years old with extensive local tumor invasion, lateral lymph node, or distant metastases at diagnosis and normal in all other DTC patients. J Clin Endocrinol Metab 2013; 98: 172-180.
    CrossrefSuche in Google Scholar
  • 2 Roman S, Lin R, Sosa JA. Prognosis of medullary thyroid carcinoma: demographic, clinical, and pathologic predictors of survival in 1252 cases. Cancer 2006; 107: 2134-2142.
    CrossrefPubMedSuche in Google Scholar
  • 3 Durante C, Haddy N, Baudin E. et al. 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 2006; 91: 2892-2899.
    CrossrefSuche in Google Scholar
  • 4 Bogsrud TV, Karantanis D, Nathan MA. et al. The prognostic value of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography in patients with suspected residual or recurrent medullary thyroid carcinoma. Mol Imaging Biol 2010; 12: 547-553.
    CrossrefSuche in Google Scholar
  • 5 Pryma DA, Schoder H, Gonen M. et al. Diagnostic accuracy and prognostic value of 18F-FDG PET in Hurthle cell thyroid cancer patients. J Nucl Med 2006; 47: 1260-1266.
    PubMedSuche in Google Scholar
  • 6 Robbins RJ, Wan Q, Grewal RK. et al. Real-time prognosis for metastatic thyroid carcinoma based on 2-[18F]fluoro-2-deoxy-D-glucose-positron emission tomography scanning. J Clin Endocrinol Metab 2006; 91: 498-505.
    CrossrefSuche in Google Scholar
  • 7 Wang W, Larson SM, Fazzari M. et al. Prognostic value of [18F]fluorodeoxyglucose positron emission tomographic scanning in patients with thyroid cancer. J Clin Endocrinol Metab 2000; 85: 1107-1113.
    PubMedSuche in Google Scholar
  • 8 Kloos RT, Eng C, Evans DB. et al. Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid 2009; 19: 565-612.
    CrossrefSuche in Google Scholar
  • 9 Meijer JA, le Cessie S, van den Hout WB. et al. Calcitonin and CEA doubling times as prognostic factors in medullary thyroid carcinoma, a structured meta-analysis. Clin Endocrinol 2010; 72: 534-542.
    CrossrefSuche in Google Scholar
  • 10 Miyauchi A, Kudo T, Miya A. et al. Prognostic impact of serum thyroglobulin doubling-time under thyrotropin suppression in patients with papillary thyroid carcinoma who underwent total thyroidectomy. Thyroid 2011; 21: 707-716.
    CrossrefSuche in Google Scholar
  • 11 Elisei R, Ugolini C, Viola D. et al. BRAF(V600E) mutation and outcome of patients with papillary thyroid carcinoma: a 15-year median follow-up study. J Clin Endocrinol Metab 2008; 93: 3943-3949.
    CrossrefSuche in Google Scholar
  • 12 Yang K, Wang H, Liang Z. et al. BRAFV600E mutation associated with non-radioiodine-avid status in distant metastatic papillary thyroid carcinoma. Clin Nucl Med 2014; 39: 675-679.
    CrossrefSuche in Google Scholar
  • 13 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: 682-687.
    CrossrefSuche in Google Scholar
  • 14 Zedenius J, Larsson C, Bergholm U. et al. Mutations of codon 918 in the RET proto-oncogene correlate to poor prognosis in sporadic medullary thyroid carcinomas. J Clin Endocrinol Metab 1995; 80: 3088-3090.
    Suche in Google Scholar
  • 15 Cooper DS, Doherty GM, Haugen BR. et al. Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2006; 16: 109-142.
    CrossrefSuche in Google Scholar
  • 16 Kondo T, Ezzat S, Asa SL. Pathogenetic mechanisms in thyroid follicular-cell neoplasia. Nature Rev Cancer 2006; 6: 292-306.
    CrossrefSuche in Google Scholar
  • 17 Sherman SI. Early clinical studies of novel therapies for thyroid cancers. Endocrinol Metab Clin North Am 2008; 37: 511-524.
    CrossrefPubMedSuche in Google Scholar
  • 18 Matsui J, Yamamoto Y, Funahashi Y. et al. E7080, a novel inhibitor that targets multiple kinases, has potent antitumor activities against stem cell factor producing human small cell lung cancer H146, based on angiogenesis inhibition. Int J Cancer 2008; 122: 664-671.
    CrossrefSuche in Google Scholar
  • 19 Kumar R, Knick VB, Rudolph SK. et al. Pharmacokinetic-pharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity. Mol Cancer Ther 2007; 6: 2012-2021.
    CrossrefSuche in Google Scholar
  • 20 Wilhelm SM, Carter C, Tang L. et al. 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 2004; 64: 7099-7109.
    CrossrefSuche in Google Scholar
  • 21 Kim DW, Jo YS, Jung HS. et al. 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 2006; 91: 4070-4076.
    CrossrefSuche in Google Scholar
  • 22 Chow LQ, Eckhardt SG. Sunitinib: from rational design to clinical efficacy. J Clin Oncol 2007; 25: 884-896.
    CrossrefSuche in Google Scholar
  • 23 Herbst RS, Heymach JV, O’Reilly MS. et al. Vandetanib (ZD6474): an orally available receptor tyrosine kinase inhibitor that selectively targets pathways critical for tumor growth and angiogenesis. Expert Opin Investig Drugs 2007; 16: 239-249.
    CrossrefSuche in Google Scholar
  • 24 Wedge SR, Ogilvie DJ, Dukes M. et al. ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration. Cancer Res 2002; 62: 4645-4655.
    PubMedSuche in Google Scholar
  • 25 Schlumberger M, Tahara M, Wirth LJ. et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med 2015; 372: 621-630.
    CrossrefSuche in Google Scholar
  • 26 Sherman SI, Jarzab B, Cabanillas ME. et al. A phase II trial of the multitargeted kinase inhibitor E7080 in advanced radioiodine (RAI)-refractory differentiated thyroid cancer (DTC). J Clin Oncol 2011; 29 (suppl): abstr 5503.
    CrossrefSuche in Google Scholar
  • 27 Brose MS, Nutting CM, Jarzab B. et al. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet 2014; 384: 319-328.
    CrossrefSuche in Google Scholar
  • 28 Kloos RT, Ringel MD, Knopp MV. et al. Phase II trial of sorafenib in metastatic thyroid cancer. J Clin Oncol 2009; 27: 1675-1684.
    CrossrefSuche in Google Scholar
  • 29 Hoftijzer H, Heemstra KA, Morreau H. et al. Beneficial effects of sorafenib on tumor progression, but not on radioiodine uptake, in patients with differentiated thyroid carcinoma. Eur J Endocrinol 2009; 161: 923-931.
    CrossrefSuche in Google Scholar
  • 30 Gupta-Abramson V, Troxel AB. et al. Phase II trial of sorafenib in advanced thyroid cancer. J Clin Oncol 2008; 26: 4714-4719.
    CrossrefSuche in Google Scholar
  • 31 Ahmed M, Barbachano Y, Riddell A. et al. Analysis of the efficacy and toxicity of sorafenib in thyroid cancer: a phase II study in a UK based population. Eur J Endocrinol 2011; 165: 315-322.
    CrossrefSuche in Google Scholar
  • 32 Bible KC, Suman VJ, Molina JR. et al. Efficacy of pazopanib in progressive, radioiodine-refractory, metastatic differentiated thyroid cancers: results of a phase 2 consortium study. Lancet Oncol 2010; 11: 962-972.
    CrossrefSuche in Google Scholar
  • 33 Cohen EE, Needles BM, Cullen KJ, Wong SJ, Wade JL, Ivy SP. et al. Phase 2 study of sunitinib in refractory thyroid cancer. J Clin Oncol 2008; 26 abstr 6025.
    CrossrefSuche in Google Scholar
  • 34 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: 5260-5268.
    CrossrefSuche in Google Scholar
  • 35 Wells SA, Robinson BG, Gagel RF. et al. Vandetanib (VAN) in locally advanced or metastatic medullary thyroid cancer (MTC): A randomized, double-blind phase III trial (ZETA). J Clin Oncol 2010; 28 (15s): abstr 5503.
    CrossrefSuche in Google Scholar
  • 36 Wells SA, Jr Gosnell J, Gagel R. et al. Vandetanib in metastatic hereditary medullary thyroid cancer: follow-up results of an open-label phase II trial. J Clin Oncol 2007; (suppl): abstr 6018.
    Suche in Google Scholar
  • 37 Haddad RI, Krebs AD, Vasselli J. et al. A phase II open-label study of vandetanib in patients with locally advanced or metastatic hereditary medullary thyroid cancer. J Clin Oncol 2008; 26 (suppl): abstr 6024.
    CrossrefSuche in Google Scholar
  • 38 Robinson BG, Paz-Ares L, Krebs A. et al. Vandetanib (100 mg) in patients with locally advanced or metastatic hereditary medullary thyroid cancer. J Clin Endocrinol Metab 2010; 95: 2664-2671.
    CrossrefSuche in Google Scholar
  • 39 Elisei R, Schlumberger MJ, Muller SP. et al. Cabozantinib in progressive medullary thyroid cancer. J Clin Oncol 2013; 31: 3639-3646.
    CrossrefSuche in Google Scholar
  • 40 Salgia R, Sherman S, Hong DS. et al. A phase I study of XL184, a RET, VEGFR2, and MET kinase inhibitor, in patients (pts) with advanced malignancies, including pts with medullary thyroid cancer (MTC). J Clin Oncol 2008; 26 (Suppl): abstr 3522.
    CrossrefSuche in Google Scholar
  • 41 Schlumberger MJ, Elisei R, Sherman SI. et al. Phase 2 trial of motesanib diphosphate(AMG706) in patients with medullary thyroid cancer (MTC). Abstracts from the 89th Annual Meeting of the Endocrine Society, Toronto 2007.
  • 42 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: 1687-1693.
    CrossrefSuche in Google Scholar
  • 43 Lam ET, Ringel MD, Kloos RT. et al. Phase II clinical trial of sorafenib in metastatic medullary thyroid cancer. J Clin Oncol 2010; 28: 2323-2330.
    CrossrefSuche in Google Scholar
  • 44 Produktinformation Cabozantinib 2013 www.ema.europa.eu/docs/de_DE/document_library/EPAR_-_Product_Information/human/002640/WC500163703.pdf
  • 45 Schlumberger M, Brose M, Elisei R. et al. Definition and management of radioactive iodine-refractory differentiated thyroid cancer. Lancet Diabetes Endocrinol 2014; 2: 356-358.
    CrossrefSuche in Google Scholar
  • 46 Grande E, Kreissl MC, Filetti S. et al. Vandetanib in advanced medullary thyroid cancer: review of adverse event management strategies. Adv Ther 2013; 30: 945-966.
    CrossrefSuche in Google Scholar
  • 47 Kreissl MC, Jacob C, Fuhrer D. et al. Best supportive care from the conservative/non-surgical perspective and its costs in the treatment of patients with advanced medullary thyroid cancer: results of a Delphi panel. Oncol Res Treat 2014; 37: 316-322.
    CrossrefSuche in Google Scholar
  • 48 Raue F, Fassnacht M, Führer D. et al. Management des fortgeschrittenen medullären Schilddrüsenkarzinoms Therapie mit Tyrosinkinaseinhibitoren. Onkologe 2014; 6: 591-597.
    Suche in Google Scholar
  • 49 Lacouture ME, Ciccolini K, Kloos RT, Agulnik M. Overview and management of dermatologic events associated with targeted therapies for medullary thyroid cancer. Thyroid 2014; 24: 1329-1340.
    CrossrefSuche in Google Scholar
  • 50 Hoy SM. Cabozantinib: a review of its use in patients with medullary thyroid cancer. Drugs 2014; 74: 1435-1444.
    CrossrefSuche in Google Scholar
  • 51 Schlumberger M, Bastholt L, Dralle H. et al. 2012 European thyroid association guidelines for metastatic medullary thyroid cancer. Eur Thyroid J 2012; 1: 5-14.
    CrossrefPubMedSuche in Google Scholar
  • 52 Carhill AA, Cabanillas ME, Jimenez C. et al. The noninvestigational use of tyrosine kinase inhibitors in thyroid cancer: establishing a standard for patient safety and monitoring. J Clin Endocrinol Metab 2013; 98: 31-42.
    CrossrefSuche in Google Scholar
  • 53 Nishie K, Kawaguchi T, Tamiya A. et al. Epidermal growth factor receptor tyrosine kinase inhibitors beyond progressive disease: a retrospective analysis for Japanese patients with activating EGFR mutations. J Thorac Oncol 2012; 7: 1722-1727.
    CrossrefSuche in Google Scholar
  • 54 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: 2086-2094.
    CrossrefSuche in Google Scholar
  • 55 Massicotte MH, Brassard M, Claude-Desroches M. et al. Tyrosine kinase inhibitor treatments in patients with metastatic thyroid carcinomas: a retrospective study of the TUTHYREF network. Eur J Endocrinol 2014; 170: 575-582.
    CrossrefSuche in Google Scholar