title: Antitumor activity in advanced cancer patients with thymic malignancies enrolled in early clinical drug development programs (Phase I trials) at Gustave Roussy.
abstract: OBJECTIVE
  Thymic epithelial neoplasms (TENs) represent a rare entity with poor prognosis and limited systemic treatment options. The aim of this study was to assess the clinical benefit, the efficacy and toxicities of agents for patients with TEN enrolled in Phase I trials.
  
  
  METHODS
  We reviewed retrospectively patients with advanced TEN enrolled in Phase I trials at Gustave Roussy (DITEP) between 1994 and 2012. Efficacy was assessed using RECIST version 1.1.
  
  
  RESULTS
  Twenty-two treated patients were enrolled (15 with thymic carcinoma, 7 with thymoma). The median number of prior systemic therapies was 2 (0-8). The median age was 50 years (range 23-72), and 4 females were treated. Treatments received encompassed mTOR inhibitor (mTORi) in 4 of patients, antiangiogenic agents (AA) in 11 patients, and other targeted therapies in 7 patients. 18% had grade 3-4 toxicity, 85% all grade toxicity and no toxic death was reported. One patient experienced a complete response (CR) and 3 a partial response (PR); 16 patients had stable disease (median 6.6 months; range 1.0-30.7) and 2 had a progressive disease. The median overall survival was 54.5 months (95% CI 25-75.50). The median progression free survival (PFS) was 6.6 months (95% CI 1.35-11.59). Median PFS was 11.6 months for mTORi, 6.9 for AA, and 6.6 for other targeted therapies.
  
  
  CONCLUSIONS
  Phase I trials appear as a sound therapeutic option in TENs pts progressing after standard treatments. Use of AA and mTORi seem to yield a good clinical response and warrant further investigation.
authors.affiliation: Departments of Pathology.
authors.forename: M
authors.initials: M
authors.lastname: Kossai
authors.affiliation: Departments Gustave Roussy, Villejuif, France; Avicenne Hospital, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Duchemann
authors.affiliation: Departments of Cancer Medicine.
authors.forename: C
authors.initials: C
authors.lastname: Boutros
authors.affiliation: Departments of Radiology.
authors.forename: C
authors.initials: C
authors.lastname: Caramella
authors.affiliation: Departments of Drug Development (DITEP).
authors.forename: A
authors.initials: A
authors.lastname: Hollebecque
authors.affiliation: Departments of Drug Development (DITEP).
authors.forename: E
authors.initials: E
authors.lastname: Angevin
authors.affiliation: Departments of Drug Development (DITEP).
authors.forename: A
authors.initials: A
authors.lastname: Gazzah
authors.affiliation: Departments of Drug Development (DITEP).
authors.forename: R
authors.initials: R
authors.lastname: Bahleda
authors.affiliation: Departments of Drug Development (DITEP).
authors.forename: E
authors.initials: E
authors.lastname: Ileana
authors.affiliation: Departments of Drug Development (DITEP).
authors.forename: C
authors.initials: C
authors.lastname: Massard
authors.affiliation: Departments of Pathology.
authors.forename: P
authors.initials: P
authors.lastname: Vielh
authors.affiliation: Departments of Drug Development (DITEP).
authors.forename: J C
authors.initials: JC
authors.lastname: Soria
authors.affiliation: Departments of Cancer Medicine; Departments Paris-Sud University, Kremlin-Bicêtre. Electronic address: benjamin.besse@gustaveroussy.fr.
authors.forename: B
authors.initials: B
authors.lastname: Besse
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D017321:Clinical Trials, Phase I as Topic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D012189:Retrospective Studies; D016019:Survival Analysis; D013953:Thymus Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor
keywords: Antiangiogenic agents; Clinical trial; Phase I; Thymic carcinoma; Thymoma; mTor inhibitors