title: Metastatic lung disease to the central nervous system: in vitro response to chemotherapeutic agents.
abstract: BACKGROUND
  Metastatic lung disease to the central nervous system (CNS) comprises a significant percentage of cranial metastases. For those cases where chemotherapy may be of palliative or therapeutic benefit, in vitro chemoresponse testing may identify the agent(s) most likely to be effective clinically.
  
  
  METHODS
  Tumor-derived cell cultures were established from 14 surgically excised lung lesions metastatic to the CNS. In vitro chemoresponse testing was performed with a variety of anticancer agents on the tumor cells that grew out of the cultured tissue specimens. Drug concentrations and exposure times were adjusted to bracket approximate average peak plasma levels that are observed typically in vivo. For each tumor-derived cell culture, a complete dose-response curve was established for each chemotherapeutic agent tested.
  
  
  RESULTS
  Approximately 80% of the 14 tumor cell cultures had a definitive response to one or more chemotherapeutic agents in vitro, with approximately one-third of these cultures displaying a response to at least three of the drugs tested. There was considerable heterogeneity in the response of individual tumor cell cultures to the chemotherapeutic drugs. The agents that showed the highest cytotoxic response rate against the individual tumor cell cultures included lomustine, carboplatin, cisplatin and etoposide.
  
  
  CONCLUSIONS
  The tumor cells isolated from individuals with lung lesions metastatic to the brain demonstrated differential chemoresponses to the agents tested. No single agent was effective against every tumor cell culture. These data suggest that in vitro chemoresponse testing of cultured tumor cells may be useful to identify biologically effective chemotherapeutic agents for individual patients, thereby addressing at least one factor in this complex therapeutic challenge.
authors.affiliation: Infectious Diseases Division, Department of Medicine, University of Pittsburgh, Scaife Hall, PA, USA.
authors.forename: Jane W
authors.initials: JW
authors.lastname: Marsh
authors.forename: Maryann
authors.initials: M
authors.lastname: Donovan
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burholt
authors.forename: Lisa D
authors.initials: LD
authors.lastname: George
authors.forename: Paul L
authors.initials: PL
authors.lastname: Kornblith
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000556:secondary; D000231:Adenocarcinoma, Papillary / Q000473:pathology / Q000556:secondary; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D016190:Carboplatin / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000556:secondary; D016543:Central Nervous System Neoplasms / Q000473:pathology* / Q000556:secondary*; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008130:Lomustine / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide; D008130:Lomustine; D016190:Carboplatin; D002945:Cisplatin