A phase II evaluation of belinostat and carboplatin in the treatment of recurrent or persistent platinum-resistant ovarian, fallopian tube, or primary peritoneal carcinoma: a Gynecologic Oncology Group study

Gynecol Oncol. 2012 May;125(2):367-71. doi: 10.1016/j.ygyno.2012.02.019. Epub 2012 Feb 21.

Abstract

Background: Patients with recurrent ovarian cancer have limited options, especially in the context of relapse less than six months from primary platinum-based therapy. This Gynecologic Oncology Group (GOG) study was conducted to evaluate the impact of the histone deacetylase inhibitor, belinostat, in combination with carboplatin in women with platinum-resistant ovarian cancer.

Methods: Eligible patients had measurable, recurrent disease within six months of their last dose of a platinum-based combination. Belinostat was dosed at 1000 mg/m(2) daily for five days with carboplatin AUC 5 on day three of 21-day cycles. The primary endpoint was overall response rate (ORR), using a two-stage design.

Results: Twenty-nine women enrolled on study and 27 were evaluable. The median number of cycles given was two (range 1-10). One patient had a complete response and one had a partial response, for an ORR of 7.4% (95% CI, .9%-24.3%). Twelve patients had stable disease while eight had increasing disease. Response could not be assessed in five (18.5%). Grade 3 and 4 events occurring in more than 10% of treated patients were uncommon and limited to neutropenia (22.2%), thrombocytopenia (14.8%), and vomiting (11.1%). The median progression-free survival (PFS) was 3.3 months and overall survival was 13.7 months. PFS of at least six months was noted in 29.6% of patients. Due to the lack of drug activity, the study was closed after the first-stage.

Conclusions: The addition of belinostat to carboplatin had little activity in a population with platinum-resistant ovarian cancer.

Publication types

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

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Carboplatin / adverse effects
  • Disease-Free Survival
  • Drug Resistance, Neoplasm
  • Fallopian Tube Neoplasms / drug therapy*
  • Female
  • Humans
  • Hydroxamic Acids / administration & dosage
  • Hydroxamic Acids / adverse effects
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Ovarian Neoplasms / drug therapy*
  • Peritoneal Neoplasms / drug therapy*
  • Sulfonamides

Substances

  • Hydroxamic Acids
  • Sulfonamides
  • Carboplatin
  • belinostat