title: Sorafenib for the Treatment of Progressive Metastatic Medullary Thyroid Cancer: Efficacy and Safety Analysis.
abstract: BACKGROUND
  Treatment of advanced medullary thyroid carcinoma (MTC) was recently improved with the approval of vandetanib and cabozantinib. However, there is still a need to explore sequential therapy with more than one tyrosine kinase inhibitor (TKI) and to explore alternative therapies when vandetanib and cabozantinib are not available. This study reports the authors' experience with sorafenib as a treatment for advanced MTC.
  
  
  METHODS
  This is a retrospective longitudinal study of 13 patients with progressive metastatic MTC treated with sorafenib 400 mg twice daily between December 2011 and January 2015. The primary endpoints were to evaluate response and progression-free survival (PFS) in patients treated with sorafenib outside a clinical trial. The secondary endpoint was an assessment of the toxicity profile. One patient was excluded because of a serious allergic skin rash one week after starting sorafenib.
  
  
  RESULTS
  The analysis included 12 patients with metastatic MTC (median age 48 years), 10 with sporadic and 2 with hereditary disease. The median duration of treatment was 11 months, and the median follow-up was 15.5 months. At data cutoff, 2/12 (16%) patients were still on treatment for 16 and 34 months. According to Response Evaluation Criteria in Solid Tumors analysis, 10 (83.3%) patients showed stable disease, and two (16.6%) had progression of disease; no partial response was observed. The median PFS was nine months. However, three patients with extensive and rapidly progressive disease died within three months of sorafenib treatment. The median PFS excluding these three patients was 12 months. Adverse events (AE) occurred in nine (75%) patients. The main AEs were skin toxicity, weight loss, and fatigue. Five (41.6%) patients needed dose reduction, and one patient discontinued treatment because of toxicity.
  
  
  CONCLUSIONS
  Treatment with sorafenib in progressive metastatic MTC is well tolerated and resulted in disease control and durable clinical benefit in 75% of patients. Sorafenib treatment could be considered when vandetanib and cabozantinib are not available or after failing these drugs.
authors.affiliation: 1 Endocrinology Department; Instituto do Câncer do Estado de São Paulo , Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil .
authors.forename: Luciana Audi
authors.initials: LA
authors.lastname: de Castroneves
authors.affiliation: 2 Medical Oncology Department; Instituto do Câncer do Estado de São Paulo , Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil .
authors.forename: Marcelo Vailati
authors.initials: MV
authors.lastname: Negrão
authors.affiliation: 3 Radiology Department; Instituto do Câncer do Estado de São Paulo , Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil .
authors.forename: Ricardo Miguel Costa
authors.initials: RM
authors.lastname: de Freitas
authors.affiliation: 1 Endocrinology Department; Instituto do Câncer do Estado de São Paulo , Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil .
authors.forename: Carla
authors.initials: C
authors.lastname: Papadia
authors.affiliation: 4 Endocrinology Department, Irmandade da Santa Casa da Misericórdia de São Paulo , São Paulo, Brazil .
authors.forename: José Viana
authors.initials: JV
authors.lastname: Lima
authors.affiliation: 5 Intensive Care Unit; Instituto do Câncer do Estado de São Paulo , Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil .
authors.forename: Julia T
authors.initials: JT
authors.lastname: Fukushima
authors.affiliation: 6 Faculdade de Medicina da Universidade de São Paulo , São Paulo, Brazil .
authors.forename: Eduardo Furquim
authors.initials: EF
authors.lastname: Simão
authors.affiliation: 7 Head and Neck Surgery Department; Instituto do Câncer do Estado de São Paulo , Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil .
authors.forename: Marco Aurélio Vamondes
authors.initials: MA
authors.lastname: Kulcsar
authors.affiliation: 8 Head and Neck Surgery Department; Hospital das Clínicas , Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil .
authors.forename: Marcos Roberto
authors.initials: MR
authors.lastname: Tavares
authors.affiliation: 9 Genetics Endocrinology LIM 25; Hospital das Clínicas , Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil .
authors.forename: Alexander Augusto de Lima
authors.initials: AA
authors.lastname: Jorge
authors.affiliation: 2 Medical Oncology Department; Instituto do Câncer do Estado de São Paulo , Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil .
authors.forename: Gilberto
authors.initials: G
authors.lastname: de Castro
authors.affiliation: 2 Medical Oncology Department; Instituto do Câncer do Estado de São Paulo , Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil .
authors.forename: Paulo Marcelo
authors.initials: PM
authors.lastname: Hoff
authors.affiliation: 1 Endocrinology Department; Instituto do Câncer do Estado de São Paulo , Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil .
authors.forename: Ana Oliveira
authors.initials: AO
authors.lastname: Hoff
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018278:Carcinoma, Neuroendocrine / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000556:secondary; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; 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*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D000077157:Sorafenib; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib