title: Weekly AUC2 carboplatin in acquired platinum-resistant ovarian cancer with or without oral phenoxodiol, a sensitizer of platinum cytotoxicity: the phase III OVATURE multicenter randomized study.
abstract: BACKGROUND
  Platinum-resistant ovarian cancer (PROC) constitutes a therapeutic dilemma with limited efficacy from traditional cytotoxic agents. Based on prior data suggesting that scheduling alterations of platinum would increase activity, the aim of the present study was to assess the potential therapeutic benefit of phenoxodiol (PXD), a novel biomodulator shown to have chemoresistance reversing potential, when combined with weekly AUC2-carboplatin in PROC patients.
  
  
  METHODS
  A multicenter randomized double-blind placebo controlled phase-III-study was conducted to compare oral PXD plus AUC2-carboplatin (group 1) versus placebo plus AUC2-carboplatin (group 2) weekly in PROC patients. The primary end point was progression-free-survival (PFS). Secondary objectives included overall survival (OS), response rates, duration of response and quality of life.
  
  
  RESULTS
  The study was terminated early 14 April 2009, after recruitment of 142 patients due to feasibility and recruitment challenges. A total of 142 patients were randomized. The groups were well balanced in terms of important baseline characteristics. The median PFS for group 1 was 15.4 weeks [95% confidence interval (CI) 11.1-21.0] versus 20.1 weeks for group 2 (95% CI = 13.1-33.4); P = 0.3. The objective response rate and median survival in group 1 versus group 2 was 0% versus 1% and 38.3 weeks (95% CI 32.0-45.3) versus 45.7 weeks (95% CI 35.6-58.0), respectively. PXD appeared to be well tolerated. The main reason for dose modification in both groups was hematologic toxicity.
  
  
  CONCLUSIONS
  Orally delivered PXD showed no evidence of clinical activity, when combined with weekly AUC2-carboplatin in PROC. In addition, single-agent weekly AUC2-carboplatin appeared to be inactive by response criteria in a homogenously defined population of PROC. This has implications for the design of future studies.
authors: Ovarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, UK.
authors: C
authors: C
authors: Fotopoulou
authors: I
authors: I
authors: Vergote
authors: P
authors: P
authors: Mainwaring
authors: M
authors: M
authors: Bidzinski
authors: J B
authors: JB
authors: Vermorken
authors: S A
authors: SA
authors: Ghamande
authors: P
authors: P
authors: Harnett
authors: S A
authors: SA
authors: Del Prete
authors: J A
authors: JA
authors: Green
authors: M
authors: M
authors: Spaczynski
authors: S
authors: S
authors: Blagden
authors: M
authors: M
authors: Gore
authors: J
authors: J
authors: Ledermann
authors: S
authors: S
authors: Kaye
authors: H
authors: H
authors: Gabra
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007529:Isoflavones / Q000008:administration & dosage; D008875:Middle Aged; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000188:drug therapy* / Q000401:mortality; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D016016:Proportional Hazards Models; D011788:Quality of Life; D016896:Treatment Outcome
chemical_list: D007529:Isoflavones; C471183:phenoxodiol; D016190:Carboplatin
keywords: carboplatin; ovarian cancer relapse; phenoxodiol; platinum resistance; reversal; survival