title: Management of advanced medullary thyroid cancer.
abstract: Medullary thyroid cancer arises from calcitonin-producing C-cells and accounts for 3-5% of all thyroid cancers. The discovery of a locally advanced medullary thyroid cancer that is not amenable to surgery or of distant metastases needs careful work-up, including measurement of serum calcitonin and carcinoembryonic antigen (and their doubling times), in addition to comprehensive imaging to determine the extent of the disease, its aggressiveness, and the need for any treatment. In the past, cytotoxic chemotherapy was used for treatment but produced little benefit. For the past 10 years, tyrosine kinase inhibitors targeting vascular endothelial growth factor receptors and RET (rearranged during transfection) have been used when a systemic therapy is indicated for large tumour burden and documented disease progression. Vandetanib and cabozantinib have shown benefits on progression-free survival compared with placebo in this setting, but their toxic effect profiles need thorough clinical management in specialised centres. This Review describes the management and treatment of patients with advanced medullary thyroid cancer with emphasis on current targeted therapies and perspectives to improve patient care. Most treatment responses are transient, emphasising that mechanisms of resistance need to be better understood and that the efficacy of treatment approaches should be improved with combination therapies or other drugs that might be more potent or target other pathways, including immunotherapy.
authors.affiliation: Department of Nuclear Medicine and Endocrine Oncology, Gustave Roussy and University Paris Sud, Villejuif, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Hadoux
authors.affiliation: Department of Medical, Surgical and Neurological Sciences, University of Siena, Via Bracci, Siena, Italy.
authors.forename: Furio
authors.initials: F
authors.lastname: Pacini
authors.affiliation: Endocrinology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: R Michael
authors.initials: RM
authors.lastname: Tuttle
authors.affiliation: Department of Nuclear Medicine and Endocrine Oncology, Gustave Roussy and University Paris Sud, Villejuif, France. Electronic address: martin.schlumberger@gustaveroussy.fr.
authors.forename: Martin
authors.initials: M
authors.lastname: Schlumberger
mesh_terms: D000813:Anilides / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015415:Biomarkers; D002116:Calcitonin / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000097:blood; D018278:Carcinoma, Neuroendocrine / Q000175:diagnosis* / Q000188:drug therapy*; D018450:Disease Progression; D018572:Disease-Free Survival; D006801:Humans; D058990:Molecular Targeted Therapy; D010880:Piperidines / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; D015415:Biomarkers; D002272:Carcinoembryonic Antigen; D010880:Piperidines; D011725:Pyridines; D011799:Quinazolines; C558660:cabozantinib; D002116:Calcitonin; D040262:Receptors, Vascular Endothelial Growth Factor; C452423:vandetanib