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Metastatic lung disease to the central nervous system: in
vitro response to chemotherapeutic
agents
Jane W. Marsh, Maryann
Donovan, Dennis R. Burholt, Lisa D. George and Paul L. Kornblith
Infectious Diseases
Division, Department of Medicine, University of Pittsburgh, Scaife Hall [J.W.M.];
BioConsulting Group [M.D.]; Precision Therapeutics, Inc., Pittsburgh, PA, USA [D.R.B., L.D.G.,
P.L.K.].
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.
Key words: chemoresponse,
chemotherapy, CNS, in vitro, metastatic lung cancer
© 2004 Kluwer Academic
Publishers. Printed in the Netherlands.
Source: doi:10.1023/B:NEON.0000013486.03634.d2
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