title: Paclitaxel/carboplatin with or without belinostat as empiric first-line treatment for patients with carcinoma of unknown primary site: A randomized, phase 2 trial.
abstract: BACKGROUND
  The objective of this study was to evaluate the efficacy of belinostat, a histone deacetylase inhibitor, when added to paclitaxel/carboplatin in the empiric first-line treatment of patients with carcinoma of unknown primary site (CUP).
  
  
  METHODS
  In this randomized phase 2 trial, previously untreated patients with CUP were randomized to receive belinostat plus paclitaxel/carboplatin (group A) or paclitaxel/carboplatin alone (group B) repeated every 21 days. Patients were re-evaluated every 2 cycles, and those without disease progression continued treatment for 6 cycles. Patients in group A then continued receiving single-agent belinostat, whereas patients in group B stopped treatment. The primary endpoint was progression-free survival (PFS): The authors postulated that the addition of belinostat would improve PFS from 5 months (expected with paclitaxel/carboplatin) to 8 months.
  
  
  RESULTS
  In total, 89 patients were randomized (group A, n = 44; group B, n = 45), and the demographics and disease characteristics were balanced between the 2 groups. The addition of belinostat to paclitaxel/carboplatin did not improve PFS (group A, 5.4 months [95% confidence interval, 3.0-6.0 months]; group B, 5.3 months [95% confidence interval, 2.8-6.6 months]; P = .85). Overall survival was 12.4 months for group A versus 9.1 months for group B (P = .20). The response rate favored the belinostat group (45% vs 21%; P = .02). Belinostat resulted in a modest increase in treatment toxicity.
  
  
  CONCLUSIONS
  The addition of belinostat to paclitaxel/carboplatin did not improve the PFS of patients with CUP who were receiving first-line therapy, although the patients who received belinostat had a higher investigator-assessed response rate. Future trials in CUP should focus on specific subsets, defined either by the predicted tissue of origin or by the identification of targetable molecular abnormalities.
authors.affiliation: Sarah Cannon Research Institute and Tennessee Oncology PLLC, Nashville, Tennessee.
authors.forename: John D
authors.initials: JD
authors.lastname: Hainsworth
authors.forename: Gedske
authors.initials: G
authors.lastname: Daugaard
authors.forename: Thierry
authors.initials: T
authors.lastname: Lesimple
authors.forename: Gerdt
authors.initials: G
authors.lastname: Hübner
authors.forename: F Anthony
authors.initials: FA
authors.lastname: Greco
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Stahl
authors.forename: Christian Meyer Zum
authors.initials: CM
authors.lastname: Büschenfelde
authors.forename: Djelila
authors.initials: D
authors.lastname: Allouache
authors.forename: Nicolas
authors.initials: N
authors.lastname: Penel
authors.forename: Poul
authors.initials: P
authors.lastname: Knoblauch
authors.forename: Karim S
authors.initials: KS
authors.lastname: Fizazi
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002277:Carcinoma / Q000188:drug therapy*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects*; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage* / Q000009:adverse effects*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects*; D017211:Treatment Failure
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D013449:Sulfonamides; D016190:Carboplatin; C487081:belinostat; D017239:Paclitaxel
keywords: belinostat; carboplatin; carcinoma of unknown primary site; paclitaxel