Tyrosine kinase inhibitors including vandetanib, pralsetinib, cabozantinib, and selpercatinib significantly improve progression-free survival in patients with medullary thyroid carcinoma (MTC) that has progressed, according to a review article published in the International Journal of Molecular Sciences

A frequent and often serious adverse event associated with their use is hypertension, the researchers noted. This is rarely dose limiting, though “with increasing survival times of patients under treatment, hypertension-associated complications can be expected to be on the rise without proper medication,” they added.

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In the article, researchers led by Michael C. Kreissl, MD, from the Department of Radiology and Nuclear Medicine, Division of Nuclear Medicine at Otto von Guericke University in Magdeburg, Germany, presented safety and efficacy data about the use of tyrosine kinase inhibitors with a main focus on hypertension.

They explained that in the case of vandetanib and cabozantinib treatment, hypertension is the result of these agents targeting vascular epithelial growth factor (VEGF), which decreases the expression of nitric oxide and prostaglandin and increases the expression of endothelin-1. Treatment with rearranged during transfection (RET)-selective tyrosine kinase inhibitors also leads to hypertension but through an unknown mechanism.

“Hypertension is easy to diagnose and treat with first-line antihypertensive drugs,” the authors wrote. They added that it is important to control hypertension to prevent cardiovascular disease.

The latest results favor RET-selective tyrosine kinase inhibitors as first-line treatment, but this is not a widely recognized opinion due to a lack of data. This conclusion takes into account the greater anticancer activity and fewer variations in treatment regimen with these therapies compared to the conventional treatment regimen with vandetanib and cabozantinib. However, more hypertensive cases of a higher grade were associated with their use, and further research is needed.


Højer Wang L, Wehland M, Wise PM, et al. Cabozantinib, vandetanib, pralsetinib and selpercatinib as treatment for progressed medullary thyroid cancer with a main focus on hypertension as adverse effect. Int J Mol Sci. Published online January 24, 2023. doi:10.3390/ijms24032312