Clinical relevance of extent of extreme drug resistance in epithelial ovarian carcinoma.
OBJECTIVE
The objective of this study was to evaluate the clinical significance of the extent of extreme drug resistance (EDR) in in vitro drug resistance assays in advanced epithelial ovarian, fallopian, and primary peritoneal cancers.


METHODS
A retrospective study was conducted using the database for in vitro drug resistance assay (EDR Assay, Oncotech, Inc.) results for advanced stage ovarian cancer samples obtained at primary surgery between 1995 and 2009. In vitro drug resistance assay results were evaluated for thirteen drugs according to the following two groups: platinum and taxane (primary treatment group) vs remaining agents (secondary treatment group). Dual-resistance was then defined as at least one EDR in the primary and secondary treatment groups. Chemotherapy response and survival outcome were correlated with assay results.


RESULTS
There were 253 cases identified. Dual-resistance (n=53, 20.9%) was not associated with chemotherapy response (p=0.62) or survival outcomes (PFS, p=0.52; OS, p=0.11). Only one (0.4%) case exhibited complete EDR to all tested drugs, and 74 (29.4%) cases showed no EDR. There was no statistical correlation between total number of drugs in the EDR range and chemotherapy response (p=0.55), progression-free survival (PFS) (p=0.18), and overall survival (OS) (p=0.87). Proportion of EDR, defined as the ratio of the number of EDR drugs divided by all drugs for an individual patient, was also not related to chemotherapy response (p=0.37), PFS (p=0.13), or OS (p=0.13).


CONCLUSIONS
Presence of extreme drug resistance to multiple agents in the in vitro drug resistance assays was not associated with survival outcomes in advanced stage epithelial ovarian, fallopian, and primary peritoneal cancers.
Matsuo
Koji
K
Department of Gynecologic Oncology, M.D. Anderson Cancer Center, University of Texas, Houston, TX 77230-1439, USA.
Eno
Michele L
ML
Im
Dwight D
DD
Rosenshein
Neil B
NB
Sood
Anil K
AK
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D016190:Carboplatin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D016208:Databases, Factual; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D004847:Epithelial Cells / Q000473:pathology; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000473:pathology; D012189:Retrospective Studies
D003520:Cyclophosphamide; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin