Multiple endocrine neoplasia type 2 medical therapy: Difference between revisions
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* Thirty percent of [[medullary thyroid cancer]] patients, especially in multiple endocrine neoplasia type 2B and 2A, are not cured by [[surgery]]. They remain affected and can develop, if not already present at the time of the [[diagnosis]], distant [[metastasis]] in the [[lung]]s, [[liver]], [[bone]] and, more rarely, [[brain]]. Several studies demonstrated that conventional therapies, such as [[chemotherapy]] and [[radiotherapy]], did not determine any [[clinical]] benefit.<ref name="pmidhttp://dx.doi.org/10.1210/jc.2008-0923">{{cite journal| author=Schmoldt A, Benthe HF, Haberland G| title=Digitoxin metabolism by rat liver microsomes. | journal=Biochem Pharmacol | year= 1975 | volume= 24 | issue= 17 | pages= 1639-41 | pmid= | doi=10.1210/jc.2008-0923 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10 }} </ref><ref name="pmidhttp://dx.doi.org/10.1016/j.clon.2010.03.014">{{cite journal| author=Schmoldt A, Benthe HF, Haberland G| title=Digitoxin metabolism by rat liver microsomes. | journal=Biochem Pharmacol | year= 1975 | volume= 24 | issue= 17 | pages= 1639-41 | pmid= | doi=10.1016/j.clon.2010.03.014 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10 }} </ref> | * Thirty percent of [[medullary thyroid cancer]] patients, especially in multiple endocrine neoplasia type 2B and 2A, are not cured by [[surgery]]. They remain affected and can develop, if not already present at the time of the [[diagnosis]], distant [[metastasis]] in the [[lung]]s, [[liver]], [[bone]] and, more rarely, [[brain]]. Several studies demonstrated that conventional therapies, such as [[chemotherapy]] and [[radiotherapy]], did not determine any [[clinical]] benefit.<ref name="pmidhttp://dx.doi.org/10.1210/jc.2008-0923">{{cite journal| author=Schmoldt A, Benthe HF, Haberland G| title=Digitoxin metabolism by rat liver microsomes. | journal=Biochem Pharmacol | year= 1975 | volume= 24 | issue= 17 | pages= 1639-41 | pmid= | doi=10.1210/jc.2008-0923 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10 }} </ref><ref name="pmidhttp://dx.doi.org/10.1016/j.clon.2010.03.014">{{cite journal| author=Schmoldt A, Benthe HF, Haberland G| title=Digitoxin metabolism by rat liver microsomes. | journal=Biochem Pharmacol | year= 1975 | volume= 24 | issue= 17 | pages= 1639-41 | pmid= | doi=10.1016/j.clon.2010.03.014 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10 }} </ref> | ||
* Until few years ago, [[Patient|patients]] with advanced and progressive [[medullary thyroid cancer]] were “[[Orphan drug|orphan]]” of [[:Category:Drugs|drugs]]. Recently, developed [[molecular]] [[therapeutics]] that [[Target cell|target]] the [[RET gene|RET]] pathway have shown very promising [[Activity (chemistry)|activity]] in [[Clinical trial|clinical trials]] of [[Patient|patients]] with advanced [[medullary thyroid cancer]].<ref name="pmid22025146">{{cite journal| author=Wells SA, Robinson BG, Gagel RF, Dralle H, Fagin JA, Santoro M et al.| title=Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. | journal=J Clin Oncol | year= 2012 | volume= 30 | issue= 2 | pages= 134-41 | pmid=22025146 | doi=10.1200/JCO.2011.35.5040 | pmc=PMC3675689 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22025146 }} </ref> In the majority of cases, the [[drug]] is a multi[[tyrosine kinase inhibitor]] (TKI) with the ability to block not only [[RET gene|RET]] but also one or more of the [[vascular endothelial growth factor receptors]] ([[Vascular endothelial growth factor receptors|VEGF-R]]) as well as [[C-MET]] and/or [[C-KIT]] or [[FLT3]] and/or other [[kinases]]. [[Vandetanib]] has been recently approved both by [[Food and Drug Administration|FDA]] ([[Food and Drug Administration]]) and EMA (European [[Medical]] Agency) for the treatment of advanced and progressive [[medullary thyroid cancer]]. | * Until few years ago, [[Patient|patients]] with advanced and progressive [[medullary thyroid cancer]] were “[[Orphan drug|orphan]]” of [[:Category:Drugs|drugs]]. Recently, developed [[molecular]] [[therapeutics]] that [[Target cell|target]] the [[RET gene|RET]] pathway have shown very promising [[Activity (chemistry)|activity]] in [[Clinical trial|clinical trials]] of [[Patient|patients]] with advanced [[medullary thyroid cancer]].<ref name="pmid22025146">{{cite journal| author=Wells SA, Robinson BG, Gagel RF, Dralle H, Fagin JA, Santoro M et al.| title=Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. | journal=J Clin Oncol | year= 2012 | volume= 30 | issue= 2 | pages= 134-41 | pmid=22025146 | doi=10.1200/JCO.2011.35.5040 | pmc=PMC3675689 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22025146 }} </ref> In the majority of cases, the [[drug]] is a multi[[tyrosine kinase inhibitor]] (TKI) with the ability to block not only [[RET gene|RET]] but also one or more of the [[vascular endothelial growth factor receptors]] ([[Vascular endothelial growth factor receptors|VEGF-R]]) as well as [[C-MET]] and/or [[C-KIT]] or [[FLT3]] and/or other [[kinases]]. [[Vandetanib]] has been recently approved both by [[Food and Drug Administration|FDA]] ([[Food and Drug Administration]]) and EMA (European [[Medical]] Agency) for the treatment of advanced and progressive [[medullary thyroid cancer]]. | ||
* Other TKIs, such as [[sorafenib]], [[sunitinib]], motesanib, [[lenvatinib]], and [[cabozantinib]], are still under investigation either in official [[phase II]]/[[Phase III|III]] [[Clinical trial|clinical trials]] or in | * Other TKIs, such as [[sorafenib]], [[sunitinib]], motesanib, [[lenvatinib]], and [[cabozantinib]], are still under investigation either in official [[phase II]]/[[Phase III|III]] [[Clinical trial|clinical trials]] or in “[[off-label]]” studies. Although very promising, further studies and longer follow-up are needed to better evaluate the [[clinical]] benefits in terms of progression-free survival and overall survival as compared to the discomfort determined by the side effects which is not negligible. Among several, the most severe and intolerable side effects are [[anorexia]], [[weight loss]], and [[fatigue]], which are difficult to be controlled. Others, such as [[hypertension]] or [[skin]] lesions can be managed with standard care procedures. | ||
* [[Vandetanib]] has been recommended for the treatment of advanced [[metastatic]] [[medullary thyroid cancer]]. | * [[Vandetanib]] has been recommended for the treatment of advanced [[metastatic]] [[medullary thyroid cancer]]. | ||
====Primary Hyperparathyroidism==== | ====Primary Hyperparathyroidism==== | ||
Among [[Patient|patients]] with persistent or recurrent [[primary hyperparathyroidism]] (PHPT), the long-term oral administration of calcimimetic drugs as [[cinacalcet]] to achieve long-term reductions in serum [[calcium]] and [[parathyroid hormone]] concentration should be considered. | |||
====Radiation Therapy==== | ====Radiation Therapy==== | ||
Revision as of 20:11, 17 June 2019
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]
Overview
The mainstay of multiple endocrine neoplasia type 2 is surgery. Medical therapies for multiple endocrine neoplasia type 2 include vandetanib, external beam radiation therapy analogues, and intensity modulated radiation therapy.
Medical Therapy
The mainstay of multiple endocrine neoplasia type 2 is surgery. Medical management of multiple endocrine neoplasia type 2 depends on the type of tumor involved.
Medullary Thyroid Cancer
Pregnancy Management
- Patients should be tested for pheochromocytoma prior to a planned pregnancy. If it is a case of unplanned pregnancy, the patient should be tested for pheochromocytoma as early as possible.
Target Therapy for Persistent Medullary Thyroid Cancer
- Thirty percent of medullary thyroid cancer patients, especially in multiple endocrine neoplasia type 2B and 2A, are not cured by surgery. They remain affected and can develop, if not already present at the time of the diagnosis, distant metastasis in the lungs, liver, bone and, more rarely, brain. Several studies demonstrated that conventional therapies, such as chemotherapy and radiotherapy, did not determine any clinical benefit.[1][2]
- Until few years ago, patients with advanced and progressive medullary thyroid cancer were “orphan” of drugs. Recently, developed molecular therapeutics that target the RET pathway have shown very promising activity in clinical trials of patients with advanced medullary thyroid cancer.[3] In the majority of cases, the drug is a multityrosine kinase inhibitor (TKI) with the ability to block not only RET but also one or more of the vascular endothelial growth factor receptors (VEGF-R) as well as C-MET and/or C-KIT or FLT3 and/or other kinases. Vandetanib has been recently approved both by FDA (Food and Drug Administration) and EMA (European Medical Agency) for the treatment of advanced and progressive medullary thyroid cancer.
- Other TKIs, such as sorafenib, sunitinib, motesanib, lenvatinib, and cabozantinib, are still under investigation either in official phase II/III clinical trials or in “off-label” studies. Although very promising, further studies and longer follow-up are needed to better evaluate the clinical benefits in terms of progression-free survival and overall survival as compared to the discomfort determined by the side effects which is not negligible. Among several, the most severe and intolerable side effects are anorexia, weight loss, and fatigue, which are difficult to be controlled. Others, such as hypertension or skin lesions can be managed with standard care procedures.
- Vandetanib has been recommended for the treatment of advanced metastatic medullary thyroid cancer.
Primary Hyperparathyroidism
Among patients with persistent or recurrent primary hyperparathyroidism (PHPT), the long-term oral administration of calcimimetic drugs as cinacalcet to achieve long-term reductions in serum calcium and parathyroid hormone concentration should be considered.
Radiation Therapy
- External beam radiation therapy
- Intensity modulated radiation therapy
Contraindicated Medications
- Dopamine: D2 receptor antagonists
- Beta adrenergic receptor antagonists
References
- ↑ Schmoldt A, Benthe HF, Haberland G (1975). "Digitoxin metabolism by rat liver microsomes". Biochem Pharmacol. 24 (17): 1639–41. doi:10.1210/jc.2008-0923.
- ↑ Schmoldt A, Benthe HF, Haberland G (1975). "Digitoxin metabolism by rat liver microsomes". Biochem Pharmacol. 24 (17): 1639–41. doi:10.1016/j.clon.2010.03.014.
- ↑ Wells SA, Robinson BG, Gagel RF, Dralle H, Fagin JA, Santoro M; et al. (2012). "Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial". J Clin Oncol. 30 (2): 134–41. doi:10.1200/JCO.2011.35.5040. PMC 3675689. PMID 22025146.