title: Therapy of endocrine disease: response and toxicity of small-molecule tyrosine kinase inhibitors in patients with thyroid carcinoma: a systematic review and meta-analysis.
abstract: BACKGROUND
  Many tyrosine kinase inhibitors (TKIs) have been studied in patients with thyroid carcinoma (TC). However, the effect and toxicity of various TKIs in differentiated TC (DTC) and medullary TC (MTC) patients have not been directly compared. The aim of the present systematic review and meta-analysis was to systematically summarize response and toxicity of TKIs in TC patients.
  
  
  METHODS
  All major databases were systematically searched for publications on TKIs in TC. Primary endpoint was objective response; secondary endpoints were clinical benefit, percentage TKI dose reduction/discontinuation, hand-foot syndrome, diarrhea, and nausea/vomiting. Meta-analysis was performed using an exact likelihood approach and a logistic regression. Pooled percentages and 95% CIs were reported.
  
  
  RESULTS
  In total, 22 publications were included. For DTC patients, gefitinib induced no objective responses. Pooled percentage was highest for pazopanib, 49 (95% CI 33-64)%, and was 17 (95% CI 12-24)% for sorafenib. For MTC, gefitinib and imatinib induced no objective responses, whereas sunitinib induced objective response in 43 (95% CI 14-77)%. For vandetanib and cabozantinib, these numbers were 40 (95% CI 34-46)% and 27 (95% CI 22-32)% respectively. Clinical benefit was found in 53 (95% CI 48-59)% of DTC patients on sorafenib, and in 84 (95% CI 79-88)% and 55 (95% CI 49-61)% of MTC patients on vandetanib and cabozantinib respectively. All TKIs were associated with considerable toxicity.
  
  
  CONCLUSIONS
  The currently studied TKIs show a modest response, while side effects are not negligible. Therefore, we suggest to solely consider TKIs in TC patients with rapid progressive disease, for whom the benefits of treatment outweigh toxicity.
authors.affiliation: Department of EndocrinologyDepartment of Internal MedicineDivision of Vascular Medicine, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsDepartments of EndocrinologyMedical OncologyClinical EpidemiologyC7-99, Leiden University Medical Center, University of Leiden, PO Box 9600, 2300 RC Leiden, The Netherlands Department of EndocrinologyDepartment of Internal MedicineDivision of Vascular Medicine, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsDepartments of EndocrinologyMedical OncologyClinical EpidemiologyC7-99, Leiden University Medical Center, University of Leiden, PO Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: E N
authors.initials: EN
authors.lastname: Klein Hesselink
authors.affiliation: Department of EndocrinologyDepartment of Internal MedicineDivision of Vascular Medicine, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsDepartments of EndocrinologyMedical OncologyClinical EpidemiologyC7-99, Leiden University Medical Center, University of Leiden, PO Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: Steenvoorden
authors.affiliation: Department of EndocrinologyDepartment of Internal MedicineDivision of Vascular Medicine, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsDepartments of EndocrinologyMedical OncologyClinical EpidemiologyC7-99, Leiden University Medical Center, University of Leiden, PO Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Kapiteijn
authors.affiliation: Department of EndocrinologyDepartment of Internal MedicineDivision of Vascular Medicine, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsDepartments of EndocrinologyMedical OncologyClinical EpidemiologyC7-99, Leiden University Medical Center, University of Leiden, PO Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: E P
authors.initials: EP
authors.lastname: Corssmit
authors.affiliation: Department of EndocrinologyDepartment of Internal MedicineDivision of Vascular Medicine, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsDepartments of EndocrinologyMedical OncologyClinical EpidemiologyC7-99, Leiden University Medical Center, University of Leiden, PO Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: A N A
authors.initials: AN
authors.lastname: van der Horst-Schrivers
authors.affiliation: Department of EndocrinologyDepartment of Internal MedicineDivision of Vascular Medicine, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsDepartments of EndocrinologyMedical OncologyClinical EpidemiologyC7-99, Leiden University Medical Center, University of Leiden, PO Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: J D
authors.initials: JD
authors.lastname: Lefrandt
authors.affiliation: Department of EndocrinologyDepartment of Internal MedicineDivision of Vascular Medicine, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsDepartments of EndocrinologyMedical OncologyClinical EpidemiologyC7-99, Leiden University Medical Center, University of Leiden, PO Box 9600, 2300 RC Leiden, The Netherlands t.p.links@umcg.nl.
authors.forename: T P
authors.initials: TP
authors.lastname: Links
authors.affiliation: Department of EndocrinologyDepartment of Internal MedicineDivision of Vascular Medicine, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsDepartments of EndocrinologyMedical OncologyClinical EpidemiologyC7-99, Leiden University Medical Center, University of Leiden, PO Box 9600, 2300 RC Leiden, The Netherlands Department of EndocrinologyDepartment of Internal MedicineDivision of Vascular Medicine, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsDepartments of EndocrinologyMedical OncologyClinical EpidemiologyC7-99, Leiden University Medical Center, University of Leiden, PO Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: O M
authors.initials: OM
authors.lastname: Dekkers
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013964:Thyroid Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases