Multiple endocrine neoplasia type 2 medical therapy
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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
Medical therapies for multiple endocrine neoplasia type 2 include vandetanib, external beam radiation therapy analogues, and intensity modulated radiation therapy.
Medical Therapy
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 progressivemedullary 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
In 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 PTH concentration should be considered.
Radiation Therapy
- External beam radiation therapy
- Intensity modulated radiation therapy
Contraindicated Medications
- Dopamine D2 receptor antagonists
- Beta adrenergic receptor antagonists
Reference
- ↑ Schmoldt A, Benthe HF, Haberland G (1975). "Digitoxin metabolism by rat liver microsomes". Biochem Pharmacol. 24 (17): 1639–41. PMID http://dx.doi.org/10.1210/jc.2008-0923 Check
|pmid=value (help). - ↑ Schmoldt A, Benthe HF, Haberland G (1975). "Digitoxin metabolism by rat liver microsomes". Biochem Pharmacol. 24 (17): 1639–41. PMID http://dx.doi.org/10.1016/j.clon.2010.03.014 Check
|pmid=value (help). - ↑ 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.