title: Low drug resistance to both platinum and taxane chemotherapy on an in vitro drug resistance assay predicts improved survival in patients with advanced epithelial ovarian, fallopian and peritoneal cancer.
abstract: The objective of this study was to evaluate the role of an in vitro drug resistance assay to platinum and taxane in the management of advanced epithelial ovarian, fallopian and primary peritoneal cancer. All patients with FIGO Stage IIIc and IV who received postoperative chemotherapy with platinum and taxane for more than 4 courses after the initial cytoreductive surgery between 1995 and 2008 were evaluated. Patients who received neoadjuvant chemotherapy were not included. An in vitro drug resistance assay (EDR Assay, Oncotech, Tustin, CA) was used to determine drug resistance for each patient's tumor tissue. Level of drug resistance was described as extreme (EDR), intermediate (IDR), or low (LDR). Response to chemotherapy and survival were correlated to the EDR Assay. Of the 335 patients who underwent primary cytoreductive surgery, 173 cases met the criteria for statistical evaluation. The 58 patients (33.5%) whose tumors had LDR to both platinum and taxane had statistically improved progression-free survival and overall survival (OS) compared with the 115 patients (66.5%) who demonstrated IDR or EDR to platinum and/or taxane (5-year OS rates, 41.1% vs. 30.9%, p = 0.014). The 5-year OS rates for the 28 (16.2%) cases that had optimal cytoreduction with LDR to both platinum and taxane was significantly improved over the 62 (35.8%) cases that were suboptimally cytoreduced with IDR or EDR to platinum and/or taxane (54.1% vs. 20.4%, respectively, p < 0.001). In conclusion, LDR to both platinum and taxane chemotherapy, as determined by an in vitro drug resistance assay, independently predicts improved survival in patients with advanced epithelial ovarian, fallopian and peritoneal cancer, especially in those patients who undergo optimal primary cytoreduction.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA. koji.matsuo@gmail.com
authors.forename: Koji
authors.initials: K
authors.lastname: Matsuo
authors.forename: Virginia K
authors.initials: VK
authors.lastname: Bond
authors.forename: Michele L
authors.initials: ML
authors.lastname: Eno
authors.forename: Dwight D
authors.initials: DD
authors.lastname: Im
authors.forename: Neil B
authors.initials: NB
authors.lastname: Rosenshein
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000188:drug therapy / Q000401:mortality / Q000556:secondary; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001681:Biological Assay / Q000379:methods*; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000401:mortality / Q000556:secondary; D019008:Drug Resistance, Neoplasm; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000556:secondary; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D001952:Bridged-Ring Compounds; D009944:Organoplatinum Compounds; D043823:Taxoids; C080625:taxane