title: Sorafenib in advanced iodine-refractory differentiated thyroid cancer: efficacy, safety and exploratory analysis of role of serum thyroglobulin and FDG-PET.
abstract: BACKGROUND
  Radioactive iodine is a crucial tool for treatment of differentiated thyroid cancer (DTC). In 5% of cases, DTCs lose I-131 avidity and assume an aggressive behaviour. Treatment options for iodine-refractory DTC are limited. We report the experience of off-label use of the tyrosine kinase inhibitor sorafenib for treatment of advanced iodine-refractory DTC.
  
  
  METHODS
  Patients with progressive DTC refractory to radioactive iodine were treated with sorafenib used off-label independently from their performance status. Primary study end-points were radiological response, progression-free survival (PFS) and safety. Secondary end-points were site-specific radiological response and overall survival (OS). An exploratory analysis of the role of serum thyroglobulin (Tg) and fluorodeoxyglucose (FDG) positron emission tomography (PET) was performed.
  
  
  RESULTS
  A total of 17 patients were included in the study. Median follow-up was 15·5 months. Clinical benefit was obtained in 71% of subjects (30% partial response and 41% stable disease). Sorafenib was mostly well tolerated, but a high incidence of fatal events was reported (three patients died from severe bleeding events and two from cardiac arrest). Median PFS was 9 months. Median OS was 10 months. The best responses were observed in lymph nodes and lung. Baseline Tg levels and the Tg response to treatment were correlated to both radiological response and PFS. Baseline FDG-PET assessment and early FDG-PET response were correlated to radiological response.
  
  
  CONCLUSIONS
  Sorafenib allows morphological disease control in the majority of patients with iodine-refractory DTC. Progression-free survival and overall survival were lower than in previous studies as a consequence of the worse clinical condition of our patients. Sorafenib is mostly well tolerated but could have been responsible for the reported fatal events. Baseline Tg and the Tg response to treatment could be useful for predicting morphological response and clinical outcome. Early FDG-PET response could be helpful for the timely identification of nonresponding patients.
authors.affiliation: Department of Molecular and Clinical Endocrinology and Oncology, Federico II University of Naples, Via S. Pansini 5, Naples, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Marotta
authors.forename: Valeria
authors.initials: V
authors.lastname: Ramundo
authors.forename: Luigi
authors.initials: L
authors.lastname: Camera
authors.forename: Michela
authors.initials: M
authors.lastname: Del Prete
authors.forename: Rosa
authors.initials: R
authors.lastname: Fonti
authors.forename: Raffaella
authors.initials: R
authors.lastname: Esposito
authors.forename: Giovannella
authors.initials: G
authors.lastname: Palmieri
authors.forename: Marco
authors.initials: M
authors.lastname: Salvatore
authors.forename: Mario
authors.initials: M
authors.lastname: Vitale
authors.forename: Annamaria
authors.initials: A
authors.lastname: Colao
authors.forename: Antongiulio
authors.initials: A
authors.lastname: Faggiano
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D049268:Positron-Emission Tomography / Q000379:methods*; D012189:Retrospective Studies; D000077157:Sorafenib; D013954:Thyroglobulin / Q000097:blood*; D013964:Thyroid Neoplasms / Q000097:blood* / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D019788:Fluorodeoxyglucose F18; D009536:Niacinamide; D013954:Thyroglobulin; D000077157:Sorafenib