title: Phase II study of belinostat in patients with recurrent or refractory advanced thymic epithelial tumors.
abstract: OBJECTIVE
  Thymic epithelial tumors are rare malignancies, and there is no standard treatment for patients with advanced disease in whom chemotherapy has failed. Antitumor activity of histone deacetylase (HDAC) inhibitors in this disease has been documented, including one patient with thymoma treated with the pan-HDAC inhibitor belinostat.
  
  
  METHODS
  Patients with advanced thymic epithelial malignancies in whom at least one line of platinum-containing chemotherapy had failed were eligible for this study. Other eligibility criteria included adequate organ function and good performance status. Belinostat was administered intravenously at 1 g/m(2) on days 1 to 5 of a 21-day cycle until disease progression or development of intolerance. The primary objective was response rate in patients with thymoma.
  
  
  RESULTS
  Of the 41 patients enrolled, 25 had thymoma, and 16 had thymic carcinoma; patients had a median of two previous systemic regimens (range, one to 10 regimens). Treatment was well tolerated, with nausea, vomiting, and fatigue being the most frequent adverse effects. Two patients achieved partial response (both had thymoma; response rate, 8%; 95% CI, 2.2% to 25%), 25 had stable disease, and 13 had progressive disease; there were no responses among patients with thymic carcinoma. Median times to progression and survival were 5.8 and 19.1 months, respectively. Survival of patients with thymoma was significantly longer than that of patients with thymic carcinoma (median not reached v 12.4 months; P = .001). Protein acetylation, regulatory T-cell numbers, and circulating angiogenic factors did not predict outcome.
  
  
  CONCLUSIONS
  Belinostat has modest antitumor activity in this group of heavily pretreated thymic malignancies. However, the duration of response and disease stabilization is intriguing, and additional testing of belinostat in this disease is warranted.
authors.affiliation: Medical Oncology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA. giacconeg@mail.nih.gov
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giaccone
authors.forename: Arun
authors.initials: A
authors.lastname: Rajan
authors.forename: Arlene
authors.initials: A
authors.lastname: Berman
authors.forename: Ronan J
authors.initials: RJ
authors.lastname: Kelly
authors.forename: Eva
authors.initials: E
authors.lastname: Szabo
authors.forename: Ariel
authors.initials: A
authors.lastname: Lopez-Chavez
authors.forename: Jane
authors.initials: J
authors.lastname: Trepel
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Lee
authors.forename: Liang
authors.initials: L
authors.lastname: Cao
authors.forename: Igor
authors.initials: I
authors.lastname: Espinoza-Delgado
authors.forename: John
authors.initials: J
authors.lastname: Spittler
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Loehrer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D006877:Hydroxamic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial; D012008:Recurrence; D019233:Retreatment; D013449:Sulfonamides; D013953:Thymus Neoplasms; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D013449:Sulfonamides; C487081:belinostat