Vandetanib for the treatment of thyroid cancer: an update.

INTRODUCTION: Medullary thyroid carcinoma (MTC) is a rare endocrine malignancy accounting for a significant percentage of thyroid cancer-related fatal events. Traditional treatment modalities used in the other types of thyroid carcinomas have been proved largely ineffective in advanced MTC. Better understanding of the molecular pathways implicated in the pathogenesis of MTC has led to the development of new drugs, which are implicated in the disruption of these molecular cascades. AREAS COVERED: This review provides the latest information regarding vandetanib , a new tyrosine kinase inhibitor mainly in the treatment of MTC. A collection of available data was conducted using the PubMed database as well as the ClinicalTrials.gov website, searching for vandetanib and thyroid cancer. EXPERT OPINION: Vandetanib targets multiple cell-signaling pathways involved in the molecular pathogenesis of thyroid cancer, namely vascular endothelial growth factor receptor-2, epidermal growth factor receptor and rearranged during transfection receptor. It is an effective approach in treating advanced MTC. However, treatment toxicity issues, as well as individual patient parameters, including disease burden and progression, should be taken into consideration before initiating vandetanib treatment.

Selenium status in patients with autoimmune and non-autoimmune thyroid diseases from four European countries.

CONTEXT: Selenium supplementation has been suggested for Hashimoto thyroiditis and Graves' ophthalmopathy. Objective, Design: Our aim is to measure selenium status (p-Se, p-SePP), urine iodine (UI) levels and urine iodine/creatinine ratio (UI/C) in different thyroid diseases (n = 416) from four European countries and to compare the results between patients with and without thyroid autoimmunity. RESULTS: p-Se and p-SePP showed positive correlation and did not correlate with UI/C. Also, these measurements were higher in patients from Italy in comparison with the other countries. Austria had the lowest UI/C ratios. Selenium deficiency exists in these four European countries. Selenium status was lower in patients with Hashimoto thyroiditis and Graves' disease in comparison with non-autoimmune thyroid disease patients and did not differ between autoimmune patients with or without thyroid peroxidase antibodies. The latter correlated positively with age. CONCLUSIONS: Our findings suggest that Se supplementation might have a beneficial effect in autoimmune thyroid patients.

Pharmacokinetic evaluation of cabozantinib for the treatment of thyroid cancer.

INTRODUCTION: Conventional treatment modalities for thyroid cancer lead to complete remission in only one-third of patients with distant metastases. On the other hand, medullary thyroid cancer (MTC) and anaplastic thyroid cancer (ATC), although rare, are responsible for a significant percentage of thyroid cancer-related deaths. New treatments are needed to treat such patients. AREAS COVERED: The aim of this review is to provide the latest information on cabozantinib (CBZ), a new tyrosine kinase inhibitor (TKI) that is currently used mainly as a treatment of MTC. The authors collated data that were retrieved from a PubMed literature search. EXPERT OPINION: CBZ targets multiple cell-signaling pathways involved in the molecular pathogenesis of thyroid cancer. These are namely VEGF receptor-2, hepatocyte growth factor receptor and rearranged during transfection receptor. Furthermore, it is a drug which may be used in cases where conventional therapies (mainly for MTC) are proved ineffective or have shown poor results with a good outcome. CBZ may also be administered alone or in combination with other drugs of the same family.

Selenium and the course of mild Graves' orbitopathy.

BACKGROUND: Oxygen free radicals and cytokines play a pathogenic role in Graves' orbitopathy. METHODS: We carried out a randomized, double-blind, placebo-controlled trial to determine the effect of selenium (an antioxidant agent) or pentoxifylline (an antiinflammatory agent) in 159 patients with mild Graves' orbitopathy. The patients were given selenium (100 µg twice daily), pentoxifylline (600 mg twice daily), or placebo (twice daily) orally for 6 months and were then followed for 6 months after treatment was withdrawn. Primary outcomes at 6 months were evaluated by means of an overall ophthalmic assessment, conducted by an ophthalmologist who was unaware of the treatment assignments, and a Graves' orbitopathy-specific quality-of-life questionnaire, completed by the patient. Secondary outcomes were evaluated with the use of a Clinical Activity Score and a diplopia score. RESULTS: At the 6-month evaluation, treatment with selenium, but not with pentoxifylline, was associated with an improved quality of life (P<0.001) and less eye involvement (P=0.01) and slowed the progression of Graves' orbitopathy (P=0.01), as compared with placebo. The Clinical Activity Score decreased in all groups, but the change was significantly greater in the selenium-treated patients. Exploratory evaluations at 12 months confirmed the results seen at 6 months. Two patients assigned to placebo and one assigned to pentoxifylline required immunosuppressive therapy for deterioration in their condition. No adverse events were evident with selenium, whereas pentoxifylline was associated with frequent gastrointestinal problems. CONCLUSIONS: Selenium administration significantly improved quality of life, reduced ocular involvement, and slowed progression of the disease in patients with mild Graves' orbitopathy. (Funded by the University of Pisa and the Italian Ministry for Education, University and Research; EUGOGO Netherlands Trial Register number, NTR524.).

[Selenium and thyroidal function; the role of immunoassays].

It is well known that selenium plays a fundamental role in regulating thyroid and other functions of the human body like reproduction, autoimmunity, glucose metabolism or bone metabolism. While for thyroid function investigation, radioimmunoassays and radioimmunometric assays both key techniques of nuclear medicine are used, for selenium measurements atomic absorption spectrometry is the method of choice. Normal thyroid gland retains high selenium concentrations even under conditions of inadequate selenium supply and expresses many of the known selenocysteine-containing proteins. Adequate selenium nutrition supports efficient thyroid hormone synthesis and metabolism and protects the thyroid gland damage by excessive iodide exposure. In regions where a combined severe iodine and selenium deficiency exist, normalization of iodine supply is mandatory before initiation of selenium supplementation in order to prevent hypothyroidism. Selenium deficiency and disturbed thyroid function may develop under conditions of special dietary regimens, such as long-term total parenteral nutrition or after inadequate nutrition in children. Some investigators suggest that selenium may be a useful adjunctive treatment for autoimmune thyroid diseases, such as Hashimoto and Graves' disease. Low serum selenium levels have been associated with higher incidence of thyroid cancer, as well as with chronic illness or lomicronw triiodothyronine syndrome. These biological actions are mediated through the expression of selenoproteins, the most important being the glutathione peroxidases, the iodothyronine deiodinases, the thioredoxine reductase and the selenoprotein P. Selenium is also associated with animal proteins. Subsequently meats and seafood are dietary sources of selenium. The ingestion of large quantities of selenium may have adverse effects. It has been shown that dietary intake of about 300 micro g of selenium daily may have a toxic effect on growth hormone and insulin like growth factor-1 metabolism, as well as in the synthesis of thyroid hormones. Main adverse effects may be anorexia, diarrhea, depression, hemorrhage, liver and kidney necrosis, blindness, ataxia and respiratory disturbances. Dermatitis and CNS deficiency have also been described. It is concluded that selenium plays an important role in regulating thyroid function, as well as in the homeostasis of thyroid hormones through the action of selenoproteins, in which it incorporates as selenocystein.