Eribulin mesylate (halichondrin B analog E7389) in platinum-resistant and platinum-sensitive ovarian cancer: a 2-cohort, phase 2 study

Cancer. 2012 May 1;118(9):2403-10. doi: 10.1002/cncr.26569. Epub 2011 Sep 20.

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.

Trial registration: ClinicalTrials.gov NCT00334893.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cohort Studies
  • Disease-Free Survival
  • Drug Administration Schedule
  • Drug Resistance, Neoplasm
  • Female
  • Furans / adverse effects
  • Furans / therapeutic use*
  • Humans
  • Ketones / adverse effects
  • Ketones / therapeutic use*
  • Middle Aged
  • Neutropenia / chemically induced
  • Ovarian Neoplasms / drug therapy*
  • Paclitaxel / therapeutic use
  • Platinum
  • Recurrence
  • Retreatment
  • Tubulin Modulators / therapeutic use*

Substances

  • Furans
  • Ketones
  • Tubulin Modulators
  • Platinum
  • eribulin
  • Paclitaxel

Associated data

  • ClinicalTrials.gov/NCT00334893