Selective use of vandetanib in the treatment of thyroid cancer
Poupak Fallahi1, Flavia Di Bari2, Silvia Martina Ferrari1
1Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Abstract:
Vandetanib is a once-daily orally available tyrosine kinase inhibitor that works by blocking RET (REarranged during Transfection), vascular endothelial growth factor receptor (VEGFR-2, VEGFR-3), and epidermal growth factor receptor and to a lesser extent VEGFR-1, which are important targets in thyroid cancer (TC). It is emerging as a potentially effective option in the treatment of advanced medullary thyroid cancer (MTC) and in dedifferentiated papillary thyroid cancer not responsive to radioiodine. The most important effect of vandetanib in aggressive MTC is a prolongation of progression-free survival and a stabilization of the disease. Significant side effects have been observed with the vandetanib therapy (as fatigue, hypertension, QTc prolongation, cutaneous rash, hand-and-foot syndrome, diarrhea, etc), and severe side effects can require the suspension of the drug. Several studies are currently under way to evaluate the long-term efficacy and tolerability of vandetanib in MTC and in dedifferentiated papillary TC. The efficacy of vandetanib in patients with MTC in long-term treatments could be overcome by the resistance to the drug. However, the effectiveness of the treatment could be ameliorated by the molecular characterization of the tumor and by the possibility to test the sensitivity of primary TC cells from each subject to different tyrosine kinase inhibitor. Association studies are evaluating the effect of the association of vandetanib with other antineoplastic agents (such as irinotecan, bortezomib, etc). Further research is needed to determine the ideal therapy to obtain the best response in terms of survival and quality of life.
Insights
Vandetanib, a tyrosine kinase inhibitor, shows promise for advanced medullary thyroid cancer (MTC) by prolonging progression-free survival. However, managing side effects and potential drug resistance requires further research for optimal patient outcomes.
Area of Science:
- Oncology
- Pharmacology
Background:
- Thyroid cancer (TC) presents challenges, particularly advanced medullary thyroid cancer (MTC) and radioiodine-refractory dedifferentiated papillary TC.
- Tyrosine kinase inhibitors (TKIs) targeting RET, VEGFR, and EGFR are crucial in TC treatment.
- Vandetanib is an orally available TKI investigated for these advanced TC types.
Purpose of the Study:
- To evaluate the efficacy and tolerability of vandetanib in advanced MTC and dedifferentiated papillary TC.
- To explore factors influencing vandetanib's long-term effectiveness, including drug resistance and molecular profiling.
- To assess combination therapies involving vandetanib and other antineoplastic agents.
Main Methods:
- Review of current studies on vandetanib's use in advanced MTC and dedifferentiated papillary TC.
- Analysis of vandetanib's mechanism of action, targeting RET, VEGFR, and EGFR pathways.
- Investigation of observed side effects and strategies for managing them.
Main Results:
- Vandetanib demonstrates efficacy in prolonging progression-free survival and stabilizing disease in aggressive MTC.
- Common side effects include fatigue, hypertension, QTc prolongation, rash, hand-and-foot syndrome, and diarrhea, sometimes necessitating treatment suspension.
- Potential for drug resistance in long-term MTC treatment exists, highlighting the need for personalized approaches.
Conclusions:
- Vandetanib is a potentially effective treatment for advanced MTC and dedifferentiated papillary TC.
- Molecular characterization and sensitivity testing may optimize vandetanib's effectiveness.
- Further research into combination therapies and long-term outcomes is essential to improve survival and quality of life.
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