Kinase-Inhibitors in Iodine-Refractory Differentiated Thyroid Cancer—Focus on Occurrence, Mechanisms, and Management of Treatment-Related Hypertension

Kinase-Inhibitors in Iodine-Refractory Differentiated Thyroid Cancer—Focus on Occurrence, Mechanisms, and Management of Treatment-Related Hypertension

Differentiated thyroid cancer (DTC) usually has a good prognosis when treated conventionally with thyroidectomy, radioactive iodine (RAI) and thyroid-stimulating hormone suppression, but some tumors develop a resistance to RAI therapy, requiring alternative treatments. Sorafenib, lenvatinib and cabo...

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Autores principales: Anne Christine Kaae, Michael C. Kreissl, Marcus Krüger, Manfred Infanger, Daniela Grimm, Markus Wehland
Formato: article
Lenguaje:EN
Publicado: MDPI AG 2021
Materias:
thyroid cancer
multikinase inhibitors
sorafenib
cabozantinib
lenvatinib
adverse effects
Biology (General)
QH301-705.5
Chemistry
QD1-999
Acceso en línea:https://doaj.org/article/d3e7b9e0c59342ffacfd6a407e6d6898
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spelling oai:doaj.org-article:d3e7b9e0c59342ffacfd6a407e6d68982021-11-25T17:54:26ZKinase-Inhibitors in Iodine-Refractory Differentiated Thyroid Cancer—Focus on Occurrence, Mechanisms, and Management of Treatment-Related Hypertension10.3390/ijms2222122171422-00671661-6596https://doaj.org/article/d3e7b9e0c59342ffacfd6a407e6d68982021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12217https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Differentiated thyroid cancer (DTC) usually has a good prognosis when treated conventionally with thyroidectomy, radioactive iodine (RAI) and thyroid-stimulating hormone suppression, but some tumors develop a resistance to RAI therapy, requiring alternative treatments. Sorafenib, lenvatinib and cabozantinib are multikinase inhibitors (MKIs) approved for the treatment of RAI-refractory DTC. The drugs have been shown to improve progression-free survival (PFS) and overall survival (OS) via the inhibition of different receptor tyrosine kinases (RTKs) that are involved in tumorigenesis and angiogenesis. Both sorafenib and lenvatinib have been approved irrespective of the line of therapy for the treatment of RAI-refractory DTC, whereas cabozantinib has only been approved as a second-line treatment. Adverse effects (AEs) such as hypertension are often seen with MKI treatment, but are generally well manageable. In this review, current clinical studies will be discussed, and the toxicity and safety of sorafenib, lenvatinib and cabozantinib treatment will be evaluated, with a focus on AE hypertension and its treatment options. In short, treatment-emergent hypertension (TE-HTN) occurs with all three drugs, but is usually well manageable and leads only to a few dose modifications or even discontinuations. This is emphasized by the fact that lenvatinib is widely considered the first-line drug of choice, despite its higher rate of TE-HTN.Anne Christine KaaeMichael C. KreisslMarcus KrügerManfred InfangerDaniela GrimmMarkus WehlandMDPI AGarticlethyroid cancermultikinase inhibitorssorafenibcabozantiniblenvatinibadverse effectsBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12217, p 12217 (2021)
institution DOAJ
collection DOAJ
language EN
topic thyroid cancer
multikinase inhibitors
sorafenib
cabozantinib
lenvatinib
adverse effects
Biology (General)
QH301-705.5
Chemistry
QD1-999
spellingShingle thyroid cancer
multikinase inhibitors
sorafenib
cabozantinib
lenvatinib
adverse effects
Biology (General)
QH301-705.5
Chemistry
QD1-999
Anne Christine Kaae
Michael C. Kreissl
Marcus Krüger
Manfred Infanger
Daniela Grimm
Markus Wehland
Kinase-Inhibitors in Iodine-Refractory Differentiated Thyroid Cancer—Focus on Occurrence, Mechanisms, and Management of Treatment-Related Hypertension
description Differentiated thyroid cancer (DTC) usually has a good prognosis when treated conventionally with thyroidectomy, radioactive iodine (RAI) and thyroid-stimulating hormone suppression, but some tumors develop a resistance to RAI therapy, requiring alternative treatments. Sorafenib, lenvatinib and cabozantinib are multikinase inhibitors (MKIs) approved for the treatment of RAI-refractory DTC. The drugs have been shown to improve progression-free survival (PFS) and overall survival (OS) via the inhibition of different receptor tyrosine kinases (RTKs) that are involved in tumorigenesis and angiogenesis. Both sorafenib and lenvatinib have been approved irrespective of the line of therapy for the treatment of RAI-refractory DTC, whereas cabozantinib has only been approved as a second-line treatment. Adverse effects (AEs) such as hypertension are often seen with MKI treatment, but are generally well manageable. In this review, current clinical studies will be discussed, and the toxicity and safety of sorafenib, lenvatinib and cabozantinib treatment will be evaluated, with a focus on AE hypertension and its treatment options. In short, treatment-emergent hypertension (TE-HTN) occurs with all three drugs, but is usually well manageable and leads only to a few dose modifications or even discontinuations. This is emphasized by the fact that lenvatinib is widely considered the first-line drug of choice, despite its higher rate of TE-HTN.
format article
author Anne Christine Kaae
Michael C. Kreissl
Marcus Krüger
Manfred Infanger
Daniela Grimm
Markus Wehland
author_facet Anne Christine Kaae
Michael C. Kreissl
Marcus Krüger
Manfred Infanger
Daniela Grimm
Markus Wehland
author_sort Anne Christine Kaae
title Kinase-Inhibitors in Iodine-Refractory Differentiated Thyroid Cancer—Focus on Occurrence, Mechanisms, and Management of Treatment-Related Hypertension
title_short Kinase-Inhibitors in Iodine-Refractory Differentiated Thyroid Cancer—Focus on Occurrence, Mechanisms, and Management of Treatment-Related Hypertension
title_full Kinase-Inhibitors in Iodine-Refractory Differentiated Thyroid Cancer—Focus on Occurrence, Mechanisms, and Management of Treatment-Related Hypertension
title_fullStr Kinase-Inhibitors in Iodine-Refractory Differentiated Thyroid Cancer—Focus on Occurrence, Mechanisms, and Management of Treatment-Related Hypertension
title_full_unstemmed Kinase-Inhibitors in Iodine-Refractory Differentiated Thyroid Cancer—Focus on Occurrence, Mechanisms, and Management of Treatment-Related Hypertension
title_sort kinase-inhibitors in iodine-refractory differentiated thyroid cancer—focus on occurrence, mechanisms, and management of treatment-related hypertension
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/d3e7b9e0c59342ffacfd6a407e6d6898
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AT marcuskruger kinaseinhibitorsiniodinerefractorydifferentiatedthyroidcancerfocusonoccurrencemechanismsandmanagementoftreatmentrelatedhypertension
AT manfredinfanger kinaseinhibitorsiniodinerefractorydifferentiatedthyroidcancerfocusonoccurrencemechanismsandmanagementoftreatmentrelatedhypertension
AT danielagrimm kinaseinhibitorsiniodinerefractorydifferentiatedthyroidcancerfocusonoccurrencemechanismsandmanagementoftreatmentrelatedhypertension
AT markuswehland kinaseinhibitorsiniodinerefractorydifferentiatedthyroidcancerfocusonoccurrencemechanismsandmanagementoftreatmentrelatedhypertension
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