<p>Evaluating vandetanib in the treatment of medullary thyroid cancer: patient-reported outcomes</p>

Abstract

Medullary thyroid cancers (MTCs) are neuroendocrine tumors, which secrete calcitonin and carcinoembryonic antigen, both of which can serve as tumor markers. Extensive and accurate surgical resection is the primary treatment for MTC, whereas the use of external beam radiotherapy is limited. Moreover, since MTC is derived from thyroid parafollicular cells or C cells, it is not responsive to either radioiodine or thyroid-stimulating hormone suppression, and therefore, they cannot be considered as treatment strategies. Traditional therapies for advanced or metastatic progressive medullary thyroid cancer (pMTC) are poorly effective. Among the new approaches tested in clinical trials, targeted chemotherapies with tyrosine kinase inhibitors (TKIs) are now available and they represent effective interventions for progressive disease, with additional investigational options emerging. This paper reviews the efficacy and safety of vandetanib in patients with a pMTC, as it has been shown to improve progression-free survival (30.5 vs 19.3 months in controls). Vandetanib is approved by the FDA and EMA for symptomatic or progressive MTC in patients with unresectable locally advanced or metastatic disease in adults, adolescents, and children older than 5 years. The most common adverse events in vandetanib-treated patients are diarrhea, rash, folliculitis, nausea, QTc prolongation, hypertension, and fatigue. More data are required to deepen our knowledge on molecular biology of tumor and host defense, with the aim to achieve better prognosis and higher quality of life for affected patients.

An Unusual Case of Hypopituitarism as an Adverse Effect of Vandetanib and Remission of Breast Metastases in a Patient with Medullary Thyroid Cancer

“…Another feature that contributes to the exceptionality of this case is the patient's 9-year PFS, far superior to the PFS reported in most studies with vandetanib or other TKIs in metastatic MTC [5,14]. In addition, the complete disappearance of the breast metastatic lesions is truly unusual.…”

Nursing Management and Adverse Events in Thyroid Cancer Treatments with Tyrosine Kinase Inhibitors. A Narrative Review

“…The coated tablets are available at doses of 100 and 300 mg. The recommended dose of vandetanib is 300 mg to be taken at the same time each day, whether on a full or empty stomach [ 31 ] and its half-life is 19 days, a period of time to consider in the management of the AEs. Typically, almost all patients on treatment, experience at least one grade 1–2 AE, where 55% of them have at least one severe grade AE [ 24 , 32 ].…”

“…Cardiovascular toxicities, especially hypertension, have been reported in up to about 25% of cases [ 33 ], therefore in congenital or more severe cases of heart disease, vandetanib may be contraindicated. Other common side effects regarding the use of vandetanib include electrolyte and metabolic disturbances (particularly glycidic and hepatic), fatigue, headache, hypothyroidism and adrenal hypo [ 31 ]; less frequent AEs involve intestinal hemorrhages and gastrointestinal and tracheal fistulas [ 34 ]. Careful monitoring of heart disorders and blood pressure is particularly indicated with the use of vandetanib.…”

Metabolic Rewiring in Radiation Oncology Toward Improving the Therapeutic Ratio

“…In vitro results suggested similar molecular effects of the deguelin derivative SH-14 but less toxicity and higher solubility which potentially could be an alternative (21). Vandetanib, a FDA-approved medullary thyroid cancer therapy that inhibits EGFR (22), impairs the HIF-1 pathway by targeting the mTOR-HIF-1a-VEGF signaling axis in breast cancer cells (23) and increases survival in advanced medullary thyroid carcinoma (268). Vandetanib is able to radiosensitize and improve overall survival in xenografts (24).…”

“…Vandetanib, a FDA-approved medullary thyroid cancer therapy that inhibits EGFR ( 22 ), impairs the HIF-1 pathway by targeting the mTOR–HIF-1α–VEGF signaling axis in breast cancer cells ( 23 ) and increases survival in advanced medullary thyroid carcinoma ( 268 ). Vandetanib is able to radiosensitize and improve overall survival in xenografts ( 24 ).…”