title: Phase II trial of sorafenib in patients with advanced anaplastic carcinoma of the thyroid.
abstract: BACKGROUND
  Anaplastic thyroid cancer (ATC) is a rare but highly aggressive malignancy with a median survival of 3-5 months. The BRAF oncogene is mutated to its active form in up to 24% of ATC cases. Sorafenib is a tyrosine kinase inhibitor that acts on the RAF-1 serine/threonine kinase. In preclinical mouse models, sorafenib inhibits the growth of ATC xenografts and improves survival. No study of sorafenib in ATC has been conducted. We conducted a multi-institutional phase II trial of sorafenib in patients with ATC who had failed up to two previous therapies.
  
  
  METHODS
  The primary endpoint of the trial was the Response Evaluation Criteria In Solid Tumors (RECIST)-defined imaging response rate. Twenty patients with ATC were treated with sorafenib 400 mg twice daily.
  
  
  RESULTS
  Two of the 20 patients had a partial response (10%) and an additional 5 of 20 (25%) had stable disease. The duration of response in the two responders was 10 and 27 months, respectively. For the patients with stable disease, the median duration was 4 months (range 3-11 months). The overall median progression-free survival was 1.9 months with a median and a 1-year survival of 3.9 months and 20%, respectively. Toxicity was manageable and as previously described for sorafenib, including hypertension and skin rash.
  
  
  CONCLUSIONS
  Sorafenib has activity in ATC, but at a low frequency and similar to our previous experience with fosbretabulin. One patient with a response had previously progressed on fosbretabulin. Toxicities were both predictable and manageable.
authors.affiliation: Division of Hematology/Oncology, Seidman Cancer Center, University Hospitals , Cleveland, OH 44106, USA.
authors.forename: Panayiotis
authors.initials: P
authors.lastname: Savvides
authors.forename: Govardhanan
authors.initials: G
authors.lastname: Nagaiah
authors.forename: Pierre
authors.initials: P
authors.lastname: Lavertu
authors.forename: Pingfu
authors.initials: P
authors.lastname: Fu
authors.forename: John J
authors.initials: JJ
authors.lastname: Wright
authors.forename: Robert
authors.initials: R
authors.lastname: Chapman
authors.forename: Jay
authors.initials: J
authors.lastname: Wasman
authors.forename: Afshin
authors.initials: A
authors.lastname: Dowlati
authors.forename: Scot C
authors.initials: SC
authors.lastname: Remick
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D003875:Drug Eruptions / Q000209:etiology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; 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*; D019908:Proto-Oncogene Proteins c-raf / Q000037:antagonists & inhibitors*; D000077157:Sorafenib; D016019:Survival Analysis; D065646:Thyroid Carcinoma, Anaplastic; D013961:Thyroid Gland / Q000187:drug effects* / Q000473:pathology; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib; D019908:Proto-Oncogene Proteins c-raf