Medullary thyroid cancer: Chemotherapy and immunotherapy
- Steven I Sherman, MD
Steven I Sherman, MD
- Associate Vice Provost, Clinical Research
- Chair and Naguib Samaan Distinguished Professor in Endocrinology
- University of Texas MD Anderson Cancer Center
Medullary thyroid cancers (MTCs) are neuroendocrine tumors of thyroid parafollicular cells that do not concentrate iodine. They occur both as sporadic tumors and as components of multiple endocrine neoplasia (MEN) type 2. They secrete calcitonin and carcinoembryonic antigen (CEA), both of which can serve as tumor markers. (See "Medullary thyroid cancer: Clinical manifestations, diagnosis, and staging".)
The primary treatment for MTC is extensive and meticulous surgical resection. There is a limited role for external-beam radiotherapy. Because the neuroendocrine-derived MTC is not responsive to either radioiodine or TSH-suppression, these options are not available for treatment of progressive metastatic MTC. (See "Medullary thyroid cancer: Treatment and prognosis".)
Patients with progressive or symptomatic metastatic disease who cannot be treated by surgery or radiotherapy should be considered candidates for systemic therapy. New approaches based upon application of targeted chemotherapies are emerging as effective interventions for progressive disease, although most remain investigational. Alternatively, treatment with either cytotoxic chemotherapy or biologic response modifiers may provide some benefit for occasional patients who fail or are ineligible for targeted therapies.
Current and experimental chemotherapies for advanced medullary thyroid carcinomas will be reviewed here. Chemotherapies for differentiated and anaplastic thyroid carcinomas are discussed separately. (See "Differentiated thyroid cancer refractory to standard treatment: Chemotherapy" and "Anaplastic thyroid cancer".)
TYROSINE KINASE INHIBITORS
As in other tumors, tyrosine kinases function in medullary thyroid cancer (MTC) to stimulate tumor proliferation, angiogenesis, invasion, and metastasis. Small molecule inhibitors of select tyrosine kinases have been of interest for the treatment of advanced MTC, given the oncogenic role of inherited and somatic mutations in the tyrosine kinase RET, as well as the contributory roles of tyrosine kinases in growth factor receptors such as the vascular endothelial growth factor receptor (VEGFR) [1,2]. These drugs partially inhibit multiple kinases at nanomolar concentrations and often affect multiple signaling pathways. (See "Classification and genetics of multiple endocrine neoplasia type 2" and "Overview of angiogenesis inhibitors", section on 'Small molecule tyrosine kinase inhibitors'.)
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- TYROSINE KINASE INHIBITORS
- Side effects and their management
- Investigational tyrosine kinase inhibitors
- - Motesanib
- CYTOTOXIC AGENTS
- INVESTIGATIONAL THERAPY
- - Tumor vaccines
- - Radioimmunotherapy
- Radiolabeled octreotide
- SUGGESTED APPROACH
- SUMMARY AND RECOMMENDATIONS