title: Predictive value of in vitro assessment of cytotoxic drug activity in advanced breast cancer.
abstract: The predictive value of a short-term in vitro total cell kill assay was investigated in 37 patients with breast cancer (BC). Tumor cells were prepared from tumor samples from 17 patients with locally advanced and 20 with metastatic BC, which were treated with the FEC (5-fluorouracil, epirubicin, cyclophosphamide) regimen or a combination of epirubicin and taxane. The cells were then tested in the fluorometric microculture cytotoxicity assay (FMCA), which is based on the conversion by viable cells of fluorescein diacetate to fluorescent fluorescein, for sensitivity to the drugs given in vivo. The FMCA data were scored as low, intermediate or extreme drug resistance based on the median cell survival +/- SD for each drug and patient subset. The drug classification for each sample was then correlated to clinical outcome in terms of objective response and time to tumor progression. The FMCA significantly predicted objective tumor response with a sensitivity of 89% and a specificity of 53%. Furthermore, in patients with locally advanced BC, low drug resistance was significantly associated with longer time to progression. It is concluded that the FMCA seems to report clinically relevant cytotoxic drug sensitivity data in BC. The potential clinical role of the FMCA and similar tests is discussed.
authors.affiliation: Department of Oncology, Orebro University Hospital, Sweden. kenneth.villman@orebroil.se
authors.forename: Kenneth
authors.initials: K
authors.lastname: Villman
authors.forename: Carl
authors.initials: C
authors.lastname: Blomqvist
authors.forename: Rolf
authors.initials: R
authors.lastname: Larsson
authors.forename: Peter
authors.initials: P
authors.lastname: Nygren
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002470:Cell Survival; D003520:Cyclophosphamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D018450:Disease Progression; D000077143:Docetaxel; D004317:Doxorubicin / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D015251:Epirubicin / Q000627:therapeutic use; D005260:Female; D005470:Fluorometry; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008727:Methotrexate / Q000627:therapeutic use; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011786:Quality Control; D012189:Retrospective Studies; D043823:Taxoids / Q000627:therapeutic use; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D015251:Epirubicin; D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil; C011272:perfosfamide; D008727:Methotrexate