Topotecan in patients with BRCA-associated and sporadic platinum-resistant ovarian, fallopian tube, and primary peritoneal cancers

Gynecol Oncol. 2011 Nov;123(2):196-9. doi: 10.1016/j.ygyno.2011.07.019. Epub 2011 Aug 19.

Abstract

Objective: To evaluate the efficacy of topoisomerase I inhibitor, topotecan, in patients with recurrent BRCA+ versus BRCA- ovarian, fallopian tube, and primary peritoneal carcinomas.

Methods: A single-institution retrospective analysis of platinum-resistant patients characterized for the presence or absence of known deleterious BRCA mutations. Patients received topotecan at a dose and schedule determined by their treating physician (five day or weekly). Response rate and progression-free survival (PFS) were assessed.

Results: A total of 50 patients (9 BRCA+, 41 BRCA-) were treated with topotecan. Both groups were well balanced in terms of age, stage, grade, and number of prior therapies. All patients had high-grade serous carcinoma. The clinical benefit rate in BRCA+ and BRCA- patients was 0% and 26.8% (6 PRs, 6 SDs), respectively (p=0.18). Median PFS in BRCA+ and BRCA- pts was 1.7 months (95% CI: 1.0-2.8 months) and 2.5 months (95%CI: 1.9-2.8 months), respectively (p=0.057). Median time to best response was 1.9 months, and median response duration 2.6 months.

Conclusions: This analysis in a heavily pretreated cohort of patients fails to support the superiority of topotecan in BRCA+ platinum-resistant ovarian, fallopian tube, and primary peritoneal cancers. Further study of this class of agents, specifically in less heavily-pretreated patients, may still be warranted.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Disease-Free Survival
  • Drug Resistance, Neoplasm
  • Fallopian Tube Neoplasms / drug therapy*
  • Fallopian Tube Neoplasms / genetics
  • Fallopian Tube Neoplasms / mortality
  • Female
  • Genes, BRCA1*
  • Genes, BRCA2*
  • Humans
  • Middle Aged
  • Mutation*
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / mortality
  • Peritoneal Neoplasms / drug therapy*
  • Peritoneal Neoplasms / genetics
  • Peritoneal Neoplasms / mortality
  • Platinum / therapeutic use
  • Retrospective Studies
  • Topoisomerase I Inhibitors / therapeutic use*
  • Topotecan / therapeutic use*

Substances

  • Topoisomerase I Inhibitors
  • Platinum
  • Topotecan