title: Extreme drug resistance assay results do not influence survival in women with epithelial ovarian cancer.
abstract: OBJECTIVE
  Extreme drug resistance (EDR) assays have been used to identify chemotherapy regimens that are least likely to be of clinical benefit in the treatment of epithelial ovarian cancer (EOC). We sought to examine the impact of EDR assay-guided therapy on the outcome of patients with EOC in the primary and recurrent settings.
  
  
  METHODS
  We conducted a retrospective review of demographic, pathologic, EDR assay and clinical outcome data from 377 patients with EOC who had an assay sent at the time of their primary or subsequent cytoreductive surgeries. Multivariate analyses were performed using Cox proportional hazards method to identify and estimate the impact of independent prognostic factors on time to progression (TTP), overall survival (OS) and survival after recurrence (RS).
  
  
  RESULTS
  Increasing age was associated with a worse OS and RS (HR=1.34; 95% CI, 1.14-1.58 and HR=1.14; 95% CI, 1.00-1.31, respectively for each decade increase in age). Surgical outcome in the setting of primary or secondary cytoreduction remained an important predictor of survival. Compared with patients with microscopic residual disease, patients who were left with 0.1 to 1.0 cm and >1.0 cm residual disease had an increased risk of recurrence (HR=1.94; 95% CI, 1.33 to 2.84 and HR=3.61; 95% CI; 2.07 to 6.39, respectively) and death (HR=1.59; 95% CI, 1.03 to 2.45; and HR=2.14; 95% CI, 1.09 to 4.20, respectively). For patients who recurred, those who did not undergo secondary cytoreductive surgery and patients who were left with >1.0 cm residual had an increased risk of death compared to patients with microscopic residual (HR=2.13; 95% CI, 1.28 to 3.54; and HR=2.84; 95% CI, 1.71 to 4.71, respectively). EDR assay results analyzed for single agents or combinations of chemotherapies failed to independently predict patient outcomes no matter if the assay was performed at the time of the primary surgery or recurrence.
  
  
  CONCLUSIONS
  EDR assay results do not independently predict or alter the outcomes of patients with EOC who are treated with the current standards of primary cytoreductive surgery followed by platinum and taxane combination chemotherapy.
authors.affiliation: Division of Gynecologic Oncology, The David Geffen School of Medicine at UCLA, Los Angeles, CA 9095, USA. akaram@mednet.ucla.edu
authors.forename: Amer K
authors.initials: AK
authors.lastname: Karam
authors.forename: Jing Wang
authors.initials: JW
authors.lastname: Chiang
authors.forename: Ewina
authors.initials: E
authors.lastname: Fung
authors.forename: Vladimir
authors.initials: V
authors.lastname: Nossov
authors.forename: Beth Y
authors.initials: BY
authors.lastname: Karlan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D016190:Carboplatin / Q000494:pharmacology / Q000627:therapeutic use; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000494:pharmacology / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003520:Cyclophosphamide; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin