title: Correlation of extreme drug resistant assay results and progression-free survival following intraperitoneal chemotherapy for advanced ovarian cancer.
abstract: The aim of this study was to determine if in vitro extreme drug resistance (EDR) to platinum and/or taxane chemotherapy was predictive of patient response to intraperitoneal (I.P.) chemotherapy in patients with stage III or recurrent epithelial ovarian cancer (EOC). Fifty-six patients were retrospectively identified who underwent optimal cytoreductive surgery for primary or recurrent eOC and then received at least three cycles of either intravenous (I.V.) or I.P. chemotherapy with platinum and paclitaxel-based chemotherapy. EDR to platinum and/or paclitaxel was determined using a commercially available assay (Oncotech, Inc., Tustin, CA). The primary outcome measure was progression-free survival (PFS). Twenty-nine (52%) patients received I.P. chemotherapy and 27 (48%) received I.V. chemotherapy. The patients were well matched in terms of age, stage, grade and histology. Ten (35%) patients in the I.OP. arm and ten (37%) patients in the I.V. arm showed EDR to either platinum and/or paclitaxel. Median PFS for all I.P. chemotherapy patients was 23 months, compared with 13 months for those receiving I.V. chemotherapy (p = 0.04). Patients with EDR to platinum and/or taxane who underwent I.V. chemotherapy had a median PFS of 13.5 months, whereas those who underwent I.P. treatment had a median PFS of 15 months (p = 0.69). Median overall survival had not been reached at the time of analysis.No significant difference in PFS was noted between patients who underwent I.P. and those who underwent I.V. chemotherapy when EDR was predicted to either platinum or paclitaxel or both. These data suggest that the decision to offer I.P. chemotherapy, with the attendant increase in morbidity, in the setting of EDR to platinum and/or taxane chemotherapy, may not be beneficial. Prospective studies, preferably analyzing platinum or taxane EDR individually, are required to validate these observations.
authors.affiliation: The Kelly Gynecologic Oncology Service, The Johns Hopkins Medical Institutions, Baltimore, MD, USA. apant2@jhmi.edu
authors.forename: A C
authors.initials: AC
authors.lastname: Pant
authors.forename: T
authors.initials: T
authors.lastname: Diaz-Montes
authors.forename: E
authors.initials: E
authors.lastname: Tanner
authors.forename: S
authors.initials: S
authors.lastname: Ahmad
authors.forename: R L
authors.initials: RL
authors.lastname: Giuntoli
authors.forename: R W
authors.initials: RW
authors.lastname: Holloway
authors.forename: R E
authors.initials: RE
authors.lastname: Bristow
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D010478:Chemotherapy, Cancer, Regional Perfusion; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D017671:Platinum Compounds / Q000008:administration & dosage
chemical_list: D000970:Antineoplastic Agents; D017671:Platinum Compounds; D017239:Paclitaxel