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Articole de sinteză Jurnalul de Chirurgie, Iaşi, 2008, Vol. 4, Nr. 2 [ISSN 1584 – 9341] 11. Woltering EA, Mamikunian PM, Zietz S, et al. Effect of octreotide LAR dose and weight on octreotide blood levels in patients with neuroendocrine tumors. Pancreas. 2005; 31: 392-400. 12. Benson AlB III, Myerson RJ, Hoffman J. Carcinoid tumors of GI tract. In: Pazdur R, Coia LR, Hoskins WJ, Wagman LD, editors. Cancer management: a multidisciplinary approach. 10th edition, 2007-2008. CMP Medica Oncology; 2007. p. 306-310. 13. Modlin IM, Sandor A. An analysis of 8305 cases of carcinoid tumors. Cancer. 1997; 79(4): 813- 829. 14. Gerstle JT, Kauffman GL Jr, Koltun WA. The incidence, management, and outcome of patients with gastrointestinal carcinoids and second primary malignancies. J Am Coll Surg. 1995; 180(4): 427-432. 15. Rubin J, Ajani J, Schirmer W, et al. Octreotide acetate long-acting formulation versus open-label subcutaneous octreotide acetate in malignant carcinoid syndrome. J Clin Oncol. 1999; 17(2): 600- 606. 16. Gorden P, Comi RJ, Maton PN, et al. NIH conference. Somatostatin and somatostatin analogue (SMS 201-995) in treatment of hormone-secreting tumors of the pituitary and gastrointestinal tract and non-neoplastic diseases of the gut. Ann Intern Med. 1989; 110(1): 35-50. 17. Frank M, Klose KJ, Wied M, et al. Combination therapy with octreotide and alpha-interferon: effect on tumor growth in metastatic endocrine gastroenteropancreatic tumors. Am J Gastroenterol. 1999; 94(5): 1381-1387. 18. Norton JA. Tumors of the endocrine system. In: Chang AE, Ganz PA, Hayes DF, editors. Oncology - an evidence based approach. New York: Springer; 2006. p. 1015-1018. 19. Benson AlB. III. Carcinomas of the gastrointestinal tract. In: Skeel RT, editor, Handbook of chemotherapy. 7th edition, Philadelphia: Wolter Kluiwer/Lippincott, Williams & Wilkins; 2007. p. 369- 270. 77
Articole de sinteză Jurnalul de Chirurgie, Iaşi, 2008, Vol. 4, Nr. 2 [ISSN 1584 – 9341] PHARMACOTHERAPY IN ADVANCED THYROID CANCER Voichiţa Mogoş Clinic of Endocrinology, „St. Spiridon” Hospital Iaşi University of Medicine and Pharmacy „Gr.T.Popa” Iaşi PHARMACOTHERAPY IN ADVANCED THYROID CANCER (Abstract): Thyroid cancers are the most common carcinomas of the endocrine system. Their behavior depends of histology, extension of the disease and patients-related factors. Differentiated thyroid cancers arising from follicular epithelium may be cured with combined surgery and radioiodine therapy. In 10-15 % of cases patients may develop metastases which are cause of death. In advanced differentiated thyroid cancers of follicular origin combined therapy with radioiodine and TSH suppression may result in a long survival if metastases are still iodine avid are made iodine avid by redifferentiation therapy. Classical chemotherapy has no significant effect in differentiated advanced thyroid cancers. The knowledge regarding genes and gene products involved in cancer development, dedifferentiation, angiogenesis, tumor progression, and apoptosis allowed the development of a new arsenal of therapeutic agents designed to target these elements. Antibodies, small molecules, antisense nucleotides, and other agents directed against RET- RAF-MAPK, the main pathway of tumor initiation and growth or against other growth factors and their receptors. Most of these therapeutic agents proven to be efficient in preclinical trials and some enter into clinical trials. KEY WORDS: DIFFERENTIATED THYROID CANCER, RET–PROTOONCOGENE, ONCOGENE INHIBITORS, ANGIOGENESIS INHIBITORS, MODULATORS OF GROWTH AND APOPTOSIS. Correspondence to: Voichiţa Mogoş, MD, PhD, Professor of Endocrinology, Clinic of Endocrinology, „St. Spiridon” Hospital Iaşi, Independenţei str. No. 1, 700111, Iaşi, Romania * BACKGROUND Differentiated thyroid cancers are the most common cancers of endocrine system. Most of differentiated thyroid cancers may be effectively cured in patients with localized disease with combined surgery and ablative radioiodine therapy. 10-15 % of patients may develop distant metastases which are the cause of the disease [1]. Advanced thyroid cancer is defined as: presence of distant metastases not including cervical lymph node metastases; recurrent locally invasive disease of the neck. STAGING OF THYROID CANCER According to American Association Joint Committee on Cancer Classification, advanced thyroid cancer includes [2]: stage IV disease; stage II disease (distant metastases) in patients less than 45 years old; any occurrence of anaplastic thyroid cancer is also considered a advanced disease because of its extremely poor prognosis even after aggressive surgical resection. Distant metastases occur in 5-23 % of patients with DCT, most of them having less differentiated cancers [3]. Most important sites of metastases are [4,5]: lung - 45-49%; bone only- 24-39%; other single sites 4-8%; multiple sites – 12-19%. * received date: 20.03.2008 accepted date: 15.05.2008 78
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