Vandetanib Treatment in Patients with Metastatic Thyroid Medullary Carcinoma: Single Center Experience

Öz

Medullary thyroid carcinomas (MTC) are neuroendocrine tumors that originate from the parafollicular C cells of the thyroid gland and accounts for 5% of thyroid cancers. In our study, we aimed to evaluate the drug tolerance, adverse events and the contribution of treatment to progression in patients followed-up with the diagnosis of metastatic MTC and treated with vandetanib in our clinic. The files of 6 patients who were treated with vandetanib in our center were examined and their data were evaluated. Skin eruptions were the most common adverse event with vandetanib treatment. Elevated liver enzymes and diarrhea were other observed adverse events. Drug treatment was interrupted for twelve weeks in 4 of 5 patients who developed skin eruptions. After twelve weeks, treatment was restarted from low dose. Treatment revision was performed in one patient due to severe skin eruptions. Stable disease was reported in 4 patients receiving vandetanib treatment, and progression in 1 patient. One of our patients with progression and brain metastases died due to infection. One patient could not continue treatment because of severe skin reactions after the usage of vandetanib for 2 months and the patient could not be evaluated in terms of progression. In metastatic and / or localized advanced MTCs, vandetanib, which is known to prolong the disease-free survival period, is a treatment option that can be preferred considering the known adverse event profile. It is important to inform patients who use vandetanib about treatment related adverse events to monitor them carefully and to provide supportive therapy in case of adverse events.

Anahtar Kelimeler

• Medullary thyroid carcinomas
• vandetanib
• adverse events

Metastatik Tiroid Medüller Karsinom Olgularında Vandetanib Tedavisi: Tek Merkez Deneyimi

Öz

Medüller tiroid karsinomları (MTK) tiroid bezinin parafoliküler C hücrelerinden köken alan ve tüm tiroid kanserlerinin %5’ini oluşturan kanserlerdir. Bu çalışmada metastatik MTK tanısıyla takipli olan ve vandetanib tedavisi uygulanan hastaların ilaç uyumu, ortaya çıkan yan etkiler ve tedavinin progresyona katkısını değerlendirmeyi amaçladık. Merkezimizde takipli ve vandetanib tedavisi verilen 6 hastanın dosya-ları incelenerek verileri değerlendirildi. Vandetanib tedavisi ile en sık izlenen yan etki cilt döküntüleriydi. Karaciğer enzim yüksekliği ve diyare diğer gözlemlenen yan etkilerdi. Cilt döküntüleri gelişen 5 hastanın 4’ünde ilaç tedavisine 12 hafta ara verildi. Dört hafta takip sonra-sında düşük doz ile tedaviye tekrar başlandı. Bir hastada ciddi cilt döküntüleri nedeniyle tedavi revizyonu yapıldı. Vandetanib tedavisi alan 4 hastada stabil hastalık, 1 hastada progresyon kaydedildi. Progresyon tespit edilen ve beyin metastazları olan bir hastamız enfeksiyon nedeniy-le ex oldu. Bir hastada ise 2 ay vandetanib kullanımı sonrasında ciddi cilt reaksiyonları geliştiğinden tedaviye devam edilemedi ve bu hasta değerlendirmeye alınamadı. Metastatik ve/veya lokalize ilerlemiş MTK’lerde hastalıksız sağ kalım süresini uzattığı bilinen vandetanib, bilinen yan etki profili de göz önüne alınarak tercih edilebilecek bir tedavi seçeneğidir. Vandetanib kullanan hastaların bilgilendirilmesi, dikkatli izlemi ve yan etki gelişmesi durumunda destek tedavisinin verilmesi önem taşımaktadır.

Anahtar Kelimeler

• Medüller tiroid karsinomları
• vandetanib
• yan etki

Kaynakça

1. Referans 1 -Hundahl SA, Fleming ID, Fremgen AM, et al. A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985-1995. Cancer. 1998; 83: 2638 – 2648.
2. Referans 2 - Lakhani VT, You YN, Wells SA. The multiple endocrine neoplasia syndromes. Annu Rev Med. 2007; 58: 253 – 265.
3. Referans 3 - Kebebew E, Clark OH. Medullary thyroid cancer. Curr Treat Options, Oncol. 2000; 1 (4): 359 –367.
4. Referans 4 - Antonelli A, Fallahi P, Ferrari SM, et al. RET TKI: potential role inthyroid cancers. Curr Oncol Rep. 2012; 14 (2): 97 – 104.
5. Referans 5 - Nikiforov YE. Thyroid carcinoma: molecular pathways and therapeutic targets. Mod Pathol. 2008;21 (Suppl 2): 37 – 43.
6. Referans 6 - De Groot JW, Links TP, Plukker JT, Lips CJ, Hofstra RM. RET as a diagnostic and therapeutic target in sporadic and hereditary endocrine tumors. Endocr Rev. 2006; 27 (5): 535 – 560.
7. Referans 7 - Almeida MQ, Hoff AO. Recent advances in the molecular pathogenesis and targeted therapies of medullary thyroid carcinoma. Curr Opin Oncol. 2012; 24: 229 - 34.
8. Referans 8 - Roman S, Lin R SJ. Prognosis of medullary thyroid carcinoma. Cancer. 2006; 107: 2134 -4 2.

9. Referans 9 - Leboulleux S, Baudin E, Travagli JP, Schlumberger M. Medullary thyroid carcinoma. Clin Endocrinol (Oxf). 2004; 61: 299 - 310
10. Referans 10 -Machens A, Schneyer U, Holzhausen HJ, Dralle H. Prospects of remission in medullary thyroid carcinoma according to basal calcitonin level. J Clin Endocrinol Metab. 2005; 90: 2029 - 34.
11. Referans 11 - Fromigué J, De Baere T, Baudin E, Dromain C, Leboulleux S, Schlumberger M. Review: chemoembolization for liver metastases from medullary thyroid carcinoma. J Clin Endocrinol Metab. 2006; 91: 2496 - 9
12. Referans 12 - Degrauwe N, Sosa JA, Roman S, Deshpande HA. Vandetanib for the treatment of metastatic medullary thyroid cancer. Clin Med Insights Oncol. 2012; 6: 243 - 52.
13. Referans 13 - Wells SA Jr, Asa SL, Dralle H, et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015; 25 (6): 567 – 610.
14. Referans 14 - Tsang VH, Robinson BG, Learoyd DL. The safety of vandetanib for the treatment of thyroid cancer. Expert Opin Drug Saf. 2016; 15 (8): 1107 – 1113.
15. Referans 15- Resteghini C, Cavalieri S, Galbiati D, et al. Management of tyrosine kinase inhibitors (TKI) side effects in differentiated and medullary thyroid cancer patients. Best Pract Res Clin Endocrinol Metab. 2017; 31 (3): 349 – 361.
16. Referans 16 - Milling RV, Grimm D, Krüger M, et al. Pazopanib, cabozantinib,and vandetanib in the treatment of progressive medullary thyroid cancer with a special focus on the adverse effects on hypertension.Int J Mol Sci. 2018; 19 (10): E3258.
17. Referans 17 - Jasim S, Ozsari L, Habra MA. Multikinase inhibitors use in differentiated thyroid carcinoma. Biologics. 2014; 8: 281 – 291.
18. Referans 18 - Fallahi P, Ferrari SM, Santini F, et al. Sorafenib and thyroid cancer. BioDrugs. 2013 ;27 (6): 615 – 628.
19. Referans 19 - Fallahi P, Ferrari SM, Baldini E, et al. The safety and efficacy of vandetanib in the treatment of progressive medullary thyroid cancer. Expert Rev Anticancer Ther. 2016;16 (11): 1109 – 1118.
20. Referans 20 - Wells SA, Robinson BG, Gagel RF, Dralle H, Fagin JA, Santoro M, 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.
21. Referans 21 - Modigliani E, Cohen R, Campos JM, et al. Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: Results in 899 patients—The GETC Study Group, Groupe d'étude des tumeurs à calcitonine. Clin Endocrinol (Oxf) 1998; 48: 265 – 273.
22. Referans 22 - Leboulleux S, Basholt L, Fauchardiere C, et all. Vandetanib in locally advanced or metastatic differentiated thyroid cancer: a randomised, double- blind, phase 2 trial. Lancet Oncology 2012; 13 (9); 897 - 905.
23. Referans 23 - Robinson, Bruce G et al. Vandetanib (100 mg) in patients with locally advanced or metastatic hereditary medullary thyroid cancer. The Journal of Clinical Endocrinology and Metabolism vol. 95, 6 (2010): 2664 - 71.