title: Eribulin mesylate (halichondrin B analog E7389) in platinum-resistant and platinum-sensitive ovarian cancer: a 2-cohort, phase 2 study.
abstract: BACKGROUND
  Eribulin mesylate is a tubulin inhibitor with activity superior to paclitaxel in NIH:OVCAR-3 human epithelial ovarian cancer xenograft models. In this study, the authors assessed the efficacy of eribulin in platinum-resistant and platinum-sensitive recurrent ovarian cancer.
  
  
  METHODS
  Patients with recurrent, measurable epithelial ovarian cancer who had received ≤2 prior cytotoxic regimens and who had adequate organ function were enrolled into 2 separate cohorts: 1) platinum-resistant patients (who had a progression-free interval <6 months after their last platinum-based therapy) and 2) platinum-sensitive patients (who had a progression-free interval ≥6 months after their last platinum-based therapy). Eribulin 1.4 mg/m(2) was administered over 15 minutes intravenously on days 1 and 8 every 21 days. Efficacy was determined by objective response on computed tomography studies.
  
  
  RESULTS
  In the platinum-resistant cohort, 37 patients enrolled, and 36 patients were evaluable for response and toxicity. Two patients achieved a partial response (5.5%), and 16 patients (44%) had stable disease as their best response. The median progression-free survival was 1.8 months (95% confidence interval, 1.4-2.8 months). In the platinum-sensitive cohort, 37 patients enrolled, and all were evaluable for response. Seven patients achieved a partial response (19%). The median progression-free survival was 4.1 months (95% confidence interval, 2.8-5.8 months). The major toxicity was grade 3 or 4 neutropenia (42% of platinum-resistant patients; 54% of platinum-sensitive patients).
  
  
  CONCLUSIONS
  Eribulin produced an objective response in 5.5% of women with platinum-resistant, recurrent ovarian cancer and in 19% of women with platinum-sensitive disease. The median progression-free survival was 1.8 months in the platinum-resistant group and 4.1 months in the platinum-sensitive group.
authors.affiliation: Department of Medicine, Gynecologic Medical Oncology Service, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, New York 10065, USA. hensleym@mskcc.org
authors.forename: Martee L
authors.initials: ML
authors.lastname: Hensley
authors.forename: Sara
authors.initials: S
authors.lastname: Kravetz
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Jia
authors.forename: Alexia
authors.initials: A
authors.lastname: Iasonos
authors.forename: William
authors.initials: W
authors.lastname: Tew
authors.forename: Lauren
authors.initials: L
authors.lastname: Pereira
authors.forename: Paul
authors.initials: P
authors.lastname: Sabbatini
authors.forename: Christin
authors.initials: C
authors.lastname: Whalen
authors.forename: Carol A
authors.initials: CA
authors.lastname: Aghajanian
authors.forename: Corinne
authors.initials: C
authors.lastname: Zarwan
authors.forename: Suzanne
authors.initials: S
authors.lastname: Berlin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D005663:Furans / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007659:Ketones / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000627:therapeutic use; D010984:Platinum; D012008:Recurrence; D019233:Retreatment; D050257:Tubulin Modulators / Q000627:therapeutic use*; D000095662:Polyether Polyketides
chemical_list: D005663:Furans; D007659:Ketones; D017239:Paclitaxel; D010984:Platinum; D050257:Tubulin Modulators; C490954:eribulin; D000095662:Polyether Polyketides