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 Oct 20;19(10):3258. doi: 10.3390/ijms19103258.

Abstract

Medullary thyroid cancer (MTC) is a rare malignancy with a poor prognosis. First line therapy is surgery, which is the only curative method of the disease. However, in non-operable cases or with tumor progression and metastases, a systemic treatment is necessary. This form of cancer is often insensitive to conventional chemotherapy, but the use of tyrosine kinase inhibitors (TKIs), such as pazopanib, cabozantinib, and vandetanib, has shown promising results with an increase in progression-free survival and prolonged lifetime. Therefore, we focused on the pharmacological characteristics of TKIs, their mechanism of action, their application as a secondary treatment option for MTC, their efficacy as a cancer drug treatment, and reviewed the ongoing clinical trials. TKIs also act systemically causing various adverse events (AEs). One common AE of this treatment is hypertension, known to be associated with cardiovascular disease and can therefore potentially worsen the well-being of the treated patients. The available treatment strategies of drug-induced hypertension were discussed. The mechanism behind the development of hypertension is still unclear. Therefore, the treatment of this AE remains symptomatic. Thus, future studies are necessary to investigate the link between tumor growth inhibition and hypertension. In addition, optimized, individual treatment strategies should be implemented.

Keywords: VEGF; antiangiogenesis; hypertension; medullary thyroid carcinoma; tyrosine kinase inhibitors.

Publication types

  • Review

MeSH terms

  • Anilides / adverse effects*
  • Anilides / therapeutic use
  • Carcinoma, Neuroendocrine / drug therapy*
  • Cardiotoxicity / etiology
  • Humans
  • Hypertension / etiology*
  • Indazoles
  • Piperidines / adverse effects*
  • Piperidines / therapeutic use
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / therapeutic use
  • Pyridines / adverse effects*
  • Pyridines / therapeutic use
  • Pyrimidines / adverse effects*
  • Pyrimidines / therapeutic use
  • Quinazolines / adverse effects*
  • Quinazolines / therapeutic use
  • Sulfonamides / adverse effects*
  • Sulfonamides / therapeutic use
  • Thyroid Neoplasms / drug therapy*

Substances

  • Anilides
  • Indazoles
  • Piperidines
  • Protein Kinase Inhibitors
  • Pyridines
  • Pyrimidines
  • Quinazolines
  • Sulfonamides
  • cabozantinib
  • pazopanib
  • vandetanib

Supplementary concepts

  • Thyroid cancer, medullary