title: Sorafenib in metastatic thyroid cancer: a systematic review.
abstract: BACKGROUND
  Sorafenib was recently approved by the U.S. Food and Drug Administration for radioiodine-resistant metastatic differentiated thyroid cancer (DTC). In addition, two drugs (vandetanib and cabozantinib) have received U.S. Food and Drug Administration approval for use in medullary thyroid cancer (MTC). Several published phase II trials have investigated the efficacy of sorafenib in thyroid cancers, but to date, results from those studies have not been compared.
  
  
  METHODS
  A systematic review of the literature was performed to assess response rate, median progression-free survival, and adverse events associated with sorafenib therapy for metastatic thyroid cancers.
  
  
  RESULTS
  This review included seven trials involving 219 patients: 159 with DTC (papillary, follicular, and poorly differentiated), 52 with MTC, and 8 with anaplastic thyroid cancer. No study reported complete responses to treatment. Overall partial response, stable disease, and progressive disease rates were 21%, 60%, and 20%, respectively. The median progression-free survival was 18 months for patients with all subtypes of thyroid cancer. Drug was discontinued in 16% of patients because of toxicities or intolerance, and the dose was reduced in a further 56%. Side effects with an incidence ≥ 50% were hand-foot syndrome (74%), diarrhea (70%), skin rash (67%), fatigue (61%), and weight loss (57%). Deaths not related to progressive disease occurred in nearly 4% of patients.
  
  
  CONCLUSIONS
  Treatment with sorafenib in patients with progressive DTC and MTC is a promising strategy, but the adverse event rate is high, leading to a high rate of dose reduction or discontinuation. Consequently, sorafenib use in patients with metastatic thyroid cancer requires careful selection of patients and careful management of side effects.
authors.affiliation: Department of Head and Neck Surgery, Department of Biostatistics, and Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Ligy
authors.initials: L
authors.lastname: Thomas
authors.forename: Stephen Y
authors.initials: SY
authors.lastname: Lai
authors.forename: Wenli
authors.initials: W
authors.lastname: Dong
authors.forename: Lei
authors.initials: L
authors.lastname: Feng
authors.forename: Ramona
authors.initials: R
authors.lastname: Dadu
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Regone
authors.forename: Maria E
authors.initials: ME
authors.lastname: Cabanillas
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D000077157:Sorafenib; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib
keywords: Adverse effects; Chemotherapy; Response rate; Tyrosine kinase inhibitors