title: Sorafenib efficacy in thymic carcinomas seems not to require c-KIT or PDGFR-alpha mutations.
abstract: OBJECTIVE
  To retrospectively evaluate sorafenib activity and safety in patients with metastatic thymic carcinoma (TC) and to correlate outcome with c-KIT and PDGFR-alpha mutational status.
  
  
  METHODS
  Patients with metastatic thymic carcinoma treated with sorafenib after at least one prior line of chemotherapy were included. Objective response rate (ORR) and toxicity were evaluated. Analysis of c-KIT and PDGFR-alpha mutational status was performed retrospectively.
  
  
  RESULTS
  From October 2007 to August 2011, 5 patients with metastatic thymic carcinoma were evaluated. A median of 8 cycles of sorafenib (range=3-29) were administered. Two patients (40%) displayed a partial response (PR), two patients presented stable disease (SD), while one patient had progression. The median progression-free (PFS) and overall survival were 28 weeks and 92 weeks, respectively. At mutational analysis, only one patient with PR had c-KIT mutation in exon 17 and was successfully treated with sunitinib for 12 months after progression to sorafenib. No PDGFR-alpha mutations were found.
  
  
  CONCLUSIONS
  Sorafenib activity seems independent from the c-KIT and PDGFR-alpha mutational status. After progression, sequence treatment with a different tyrosine kinase inhibitor can be considered. These results are promising and need further confirmation on larger, possibly prospective, series of patients.
authors.affiliation: Department of Oncology and Advanced Technologies, Oncology Unit, Azienda Ospedaliera S.Maria Nuova/IRCCS of Reggio Emilia, Reggio Emilia, Italy pagano.maria@asmn.re.it.
authors.forename: Maria
authors.initials: M
authors.lastname: Pagano
authors.affiliation: Department of Oncology and Advanced Technologies, Oncology Unit, Azienda Ospedaliera S.Maria Nuova/IRCCS of Reggio Emilia, Reggio Emilia, Italy.
authors.forename: Nuria Maria Asensio
authors.initials: NM
authors.lastname: Sierra
authors.affiliation: Department of Oncology and Advanced Technologies, Oncology Unit, Azienda Ospedaliera S.Maria Nuova/IRCCS of Reggio Emilia, Reggio Emilia, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Panebianco
authors.affiliation: Department of Oncology and Advanced Technologies, Operative Unit of Pathology, Azienda Ospedaliera S.Maria Nuova/IRCCS of Reggio Emilia, Reggio Emilia, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Rossi
authors.affiliation: Department of Oncology and Advanced Technologies, Oncology Unit, Azienda Ospedaliera S.Maria Nuova/IRCCS of Reggio Emilia, Reggio Emilia, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Gnoni
authors.affiliation: Department of Oncology and Advanced Technologies, Oncology Unit, Azienda Ospedaliera S.Maria Nuova/IRCCS of Reggio Emilia, Reggio Emilia, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Bisagni
authors.affiliation: Department of Oncology and Advanced Technologies, Oncology Unit, Azienda Ospedaliera S.Maria Nuova/IRCCS of Reggio Emilia, Reggio Emilia, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Boni
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D012189:Retrospective Studies; D000077157:Sorafenib; D013945:Thymoma / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D013953:Thymus Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha
keywords: PDGFR alpha; Thymic carcinoma; c-KIT; sorafenib; tyrosine kinase