title: Randomized, phase II, placebo-controlled, double-blind study with and without enzastaurin in combination with paclitaxel and carboplatin as first-line treatment followed by maintenance treatment in advanced ovarian cancer.
abstract: OBJECTIVE
  Enzastaurin is an oral serine/threonine kinase inhibitor antitumor agent. Our phase II trial tested the efficacy and safety of enzastaurin added to a standard carboplatin/paclitaxel chemotherapy regimen in patients with newly diagnosed advanced ovarian cancer.
  
  
  METHODS
  This was a randomized, placebo-controlled study in patients with International Federation of Gynecology and Obstetrics stage IIB to IV ovarian, fallopian tube, or peritoneal epithelial carcinoma. Patients were randomly assigned to six cycles of chemotherapy (paclitaxel/carboplatin ± enzastaurin [PCE/PC]) followed by maintenance therapy (enzastaurin/placebo). Primary end point was progression-free survival (PFS). Secondary measures included response rate, safety assessment, and translational research.
  
  
  RESULTS
  A total of 142 patients were randomly assigned to PCE (n = 69) or PC (n = 73). Patients in the PCE group had a 3.7-month longer median PFS compared with patients in the PC group; this was not statistically significant (hazard ratio [HR], 0.80; 95% CI, 0.50 to 1.29; P = .37). Safety profiles of the treatment arms were comparable. Frequency of discontinuation because of adverse events was similar (PCE, 11.9%; PC, 9.7%). Multivariate analyses confirmed the importance of optimal debulking with regard to PFS (debulking optimal v suboptimal: HR, 0.51; 95% CI, 0.30 to 0.85; P = .009). HR for covariate stage (stage IIB to IIIB v IIIC to IV) was not statistically significant (0.75; 95% CI, 0.38 to 1.47; P = .40). Translational research of immunohistochemistry protein assays did not identify any markers significantly associated with treatment difference regarding PFS.
  
  
  CONCLUSIONS
  The PCE combination increased PFS, but it was not significantly superior to PC in this phase II study.
authors.affiliation: University Hospital, Leuven, Belgium. ignace.vergote@uzleuven.be
authors.forename: Ignace B
authors.initials: IB
authors.lastname: Vergote
authors.forename: Radoslav
authors.initials: R
authors.lastname: Chekerov
authors.forename: Frederic
authors.initials: F
authors.lastname: Amant
authors.forename: Philipp
authors.initials: P
authors.lastname: Harter
authors.forename: Antonio
authors.initials: A
authors.lastname: Casado
authors.forename: Janusz
authors.initials: J
authors.lastname: Emerich
authors.forename: Thomas
authors.initials: T
authors.lastname: Bauknecht
authors.forename: Kambiz
authors.initials: K
authors.lastname: Mansouri
authors.forename: Scott P
authors.initials: SP
authors.lastname: Myrand
authors.forename: Tuan S
authors.initials: TS
authors.lastname: Nguyen
authors.forename: Peipei
authors.initials: P
authors.lastname: Shi
authors.forename: Jalid
authors.initials: J
authors.lastname: Sehouli
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D064546:Protein Kinase C beta
chemical_list: D007211:Indoles; D016190:Carboplatin; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D017239:Paclitaxel; C504878:enzastaurin