title: A chemoresponse assay for prediction of platinum resistance in primary ovarian cancer.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Magee-Womens Hospital of University of Pittsburgh Medical Center, Pittsburgh, PA.
authors: Thomas C
authors: TC
authors: Krivak
authors: Division of Surgical Subspecialties, Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY.
authors: Shashikant
authors: S
authors: Lele
authors: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Magee-Womens Hospital of University of Pittsburgh Medical Center, Pittsburgh, PA.
authors: Scott
authors: S
authors: Richard
authors: Division of Gynecology Oncology, Department of Obstetrics and Gynecology, Duke Cancer Institute, Duke University Medical Center, Durham, NC.
authors: Angeles Alvarez
authors: AA
authors: Secord
authors: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Alabama School of Medicine at Birmingham, Birmingham, AL.
authors: Charles A
authors: CA
authors: Leath
authors: Department of Product Development, Precision Therapeutics Inc, Pittsburgh, PA.
authors: Stacey L
authors: SL
authors: Brower
authors: Department of Product Development, Precision Therapeutics Inc, Pittsburgh, PA.
authors: Chunqiao
authors: C
authors: Tian
authors: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Women and Infants Hospital, Brown University, Providence, RI.
authors: Richard G
authors: RG
authors: Moore
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D000077216:Carcinoma, Ovarian Epithelial; D017024:Chemotherapy, Adjuvant; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000209:etiology / Q000517:prevention & control*; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D017239:Paclitaxel / Q000008:administration & dosage; D011446:Prospective Studies; D012372:ROC Curve; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D016190:Carboplatin; D017239:Paclitaxel
keywords: chemoresponse assay; ovarian cancer; platinum resistance