title: A phase II evaluation of belinostat and carboplatin in the treatment of recurrent or persistent platinum-resistant ovarian, fallopian tube, or primary peritoneal carcinoma: a Gynecologic Oncology Group study.
abstract: BACKGROUND
  Patients with recurrent ovarian cancer have limited options, especially in the context of relapse less than six months from primary platinum-based therapy. This Gynecologic Oncology Group (GOG) study was conducted to evaluate the impact of the histone deacetylase inhibitor, belinostat, in combination with carboplatin in women with platinum-resistant ovarian cancer.
  
  
  METHODS
  Eligible patients had measurable, recurrent disease within six months of their last dose of a platinum-based combination. Belinostat was dosed at 1000 mg/m(2) daily for five days with carboplatin AUC 5 on day three of 21-day cycles. The primary endpoint was overall response rate (ORR), using a two-stage design.
  
  
  RESULTS
  Twenty-nine women enrolled on study and 27 were evaluable. The median number of cycles given was two (range 1-10). One patient had a complete response and one had a partial response, for an ORR of 7.4% (95% CI, .9%-24.3%). Twelve patients had stable disease while eight had increasing disease. Response could not be assessed in five (18.5%). Grade 3 and 4 events occurring in more than 10% of treated patients were uncommon and limited to neutropenia (22.2%), thrombocytopenia (14.8%), and vomiting (11.1%). The median progression-free survival (PFS) was 3.3 months and overall survival was 13.7 months. PFS of at least six months was noted in 29.6% of patients. Due to the lack of drug activity, the study was closed after the first-stage.
  
  
  CONCLUSIONS
  The addition of belinostat to carboplatin had little activity in a population with platinum-resistant ovarian cancer.
authors.affiliation: Program in Women's Oncology, Women & Infants Hospital/Alpert Medical School of Brown University, Providence, RI, United States. donstevendizon@gmail.com
authors.forename: Don S
authors.initials: DS
authors.lastname: Dizon
authors.forename: John A
authors.initials: JA
authors.lastname: Blessing
authors.forename: Richard T
authors.initials: RT
authors.lastname: Penson
authors.forename: Richard D
authors.initials: RD
authors.lastname: Drake
authors.forename: Joan L
authors.initials: JL
authors.lastname: Walker
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Johnston
authors.forename: Paul A
authors.initials: PA
authors.lastname: Disilvestro
authors.forename: Amanda Nickles
authors.initials: AN
authors.lastname: Fader
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010534:Peritoneal Neoplasms / Q000188:drug therapy*; D013449:Sulfonamides
chemical_list: D006877:Hydroxamic Acids; D013449:Sulfonamides; D016190:Carboplatin; C487081:belinostat