title: Chemosensitivity testing predicts survival in ovarian cancer.
abstract: The aim of this study was to assess the use of the MTT assay for chemosensitity testing to identify drug resistance and predict survival in patients with advanced ovarian cancer. Samples of ascitic fluid and/or solid biopsies were taken from 120 patients with FIGO stage III or IV ovarian adenocarcinoma at presentation. Cells were exposed for 48 hours to four concentrations of clinically relevant drugs including platinums, anthracyclines and alkylating agents. Cell survival was measured using the 3-4,5-dimethyl-2, 5-diphenyl tetrazolium bromide (MTT) assay allowing patients to be grouped as "sensitive" or "resistant" in vitro. Clinical data including age, residual disease, histological grade, treatment, response after initial treatment and overall survival were collected. There was a highly significant (p<0.0001) correlation of in vitro sensitivity with in vivo response in the patients who completed their therapy, with an 83% positive predictive accuracy for resistance. This translated in the longer term to an increased survival for the patients found to be sensitive in vitro to their therapy with a 5-year survival rate of 24% compared to 12% for the resistant group (p=0.033). These results suggest that MTT chemonsensitivity testing can predict response in ovarian cancer leading to the prospect of increased survival in this devastating disease by customising therapy to individual patients.
authors.affiliation: Haematology Research, Pembury Hospital, Kent, UK.
authors.forename: C G
authors.initials: CG
authors.lastname: Taylor
authors.forename: J M
authors.initials: JM
authors.lastname: Sargent
authors.forename: A W
authors.initials: AW
authors.lastname: Elgie
authors.forename: C J
authors.initials: CJ
authors.lastname: Williamson
authors.forename: G M
authors.initials: GM
authors.lastname: Lewandowicz
authors.forename: O
authors.initials: O
authors.lastname: Chappatte
authors.forename: J G
authors.initials: JG
authors.lastname: Hill
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000401:mortality*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000401:mortality*; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D015996:Survival Rate; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D004396:Coloring Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue