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

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

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.

Keywords: chemoresponse assay; ovarian cancer; platinum resistance.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Carcinoma, Ovarian Epithelial
  • Chemotherapy, Adjuvant
  • Drug Resistance, Neoplasm*
  • Female
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Recurrence, Local / etiology
  • Neoplasm Recurrence, Local / prevention & control*
  • Neoplasm Staging
  • Neoplasms, Glandular and Epithelial / drug therapy*
  • Neoplasms, Glandular and Epithelial / pathology
  • Neoplasms, Glandular and Epithelial / surgery
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / surgery
  • Paclitaxel / administration & dosage
  • Prospective Studies
  • ROC Curve
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Carboplatin
  • Paclitaxel