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Am J Obstet Gynecol. 2014 Jul;211(1):68.e1-8. doi: 10.1016/j.ajog.2014.02.009. Epub 2014 Feb 12.

A chemoresponse assay for prediction of platinum resistance in primary ovarian cancer.

Author information

  • 1Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Magee-Womens Hospital of University of Pittsburgh Medical Center, Pittsburgh, PA.
  • 2Division of Surgical Subspecialties, Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY.
  • 3Division of Gynecology Oncology, Department of Obstetrics and Gynecology, Duke Cancer Institute, Duke University Medical Center, Durham, NC.
  • 4Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Alabama School of Medicine at Birmingham, Birmingham, AL.
  • 5Department of Product Development, Precision Therapeutics Inc, Pittsburgh, PA.
  • 6Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Women and Infants Hospital, Brown University, Providence, RI.

Abstract

OBJECTIVE:

Recurrence following primary platinum-based chemotherapy remains a challenge in the treatment of patients with advanced-stage epithelial ovarian cancer. This study examines whether a chemoresponse assay can identify patients who are platinum-resistant prior to treatment.

STUDY DESIGN:

Women (n = 276) with International Federation of Gynecology and Obstetrics stage III-IV ovarian, fallopian, and peritoneal cancer were enrolled in an observational study, and the responsiveness of their tumors was evaluated using a chemoresponse assay. All patients were treated with a platinum/taxane regimen following cytoreductive surgery. Assay responses to carboplatin or paclitaxel were classified as sensitive, intermediate sensitive (IS), or resistant. Association of assay response with progression-free survival (PFS) was analyzed using the Kaplan-Meier method and a Cox regression model.

RESULTS:

Patients whose tumors were resistant to carboplatin were at increased risk of disease progression compared to those with nonresistant (sensitive + IS) tumors (median PFS: 11.8 vs 16.6 months, respectively, P < .001), and the association was confirmed after adjusting for other clinical factors (hazard ratio, 1.71; 95% confidence interval, 1.12-2.62; P = .013). Association of assay response to paclitaxel with PFS trended in multivariate analysis (hazard ratio, 1.28; 95% confidence interval, 0.84-1.95; P = .245). For tumors resistant to carboplatin, 59% were sensitive or IS to at least 1 other commonly used agent, demonstrating the ability of the assay to inform treatment decisions beyond the standard platinum/taxane regimen.

CONCLUSION:

Assay resistance to carboplatin is strongly associated with shortened PFS among advanced-stage epithelial ovarian cancer patients treated with carboplatin + paclitaxel therapy, supporting use of this assay to identify patients likely to experience early recurrence on standard platinum-based therapy.

Copyright © 2014 Mosby, Inc. All rights reserved.

KEYWORDS:

chemoresponse assay; ovarian cancer; platinum resistance

[PubMed - indexed for MEDLINE]
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