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Intralesional Mitoxantrone
Biopolymer-Mediated Chemotherapy Prolongs Survival in Rats with Experimental
Brain Tumors
Marco Saini, Florian Roser, Samii Hussein, Madjid Samii,
Mattia Bellinzona
Center
for Experimental Neuro-Oncology; Klinikum Hannover Nordstadt, Germany (M.Saini,
M.B.); Department of Neurosurgery, Klinikum Hannover
Nordstadt, Germany (F.R.,
S.H.); Department of Neurosurgery, Hannover Medical School,
Hannover, Germany and International Neuroscience Institute (M.Samii)
The present study was designed to test the efficacy of intratumoral
biopolymer-mediated mitoxantrone chemotherapy in the rat brain 9L glioma
model.
Mitoxantrone polymers were tested in vitro in 9L and C6 cell cultures
for 10 days.
Subsequently, adult Fisher 344 rats were implanted with 5 ×
104 9L glioma cells in the frontal region of the brain.
In a first experiment, 2 days after cells inoculation, one group of rats
were implanted with a biopolymer loaded with 4 mg of mitoxantrone at the tumor
site.
A second group of rats received drug-free biopolymers and served as
controls.
In a second experiment, rats were implanted with a biopolymer loaded with
2 mg of mitoxantrone.
Another group of rats received 2 mg of mitoxantrone
intraperitoneally.
Controls received drug-free biopolymers.
Rats were sacrificed as soon as they developed progressive neurological
deficits.
In the first experiment mean survival of mitoxantrone-treated rats was 10
± 2 vs. 15 ± 2
days for the control group (P = 0.0003).
Early morbidity was seen in 60%, and impaired wound healing was seen in
40% of the 4 mg mitoxantrone treated animals.
In the second experiment mean survival of mitoxantrone-treated rats was
significantly longer than that of the control group (P < 0.0001)
with 33 ± 7 vs. 13.8 ±
2 days for the control group.
Only transient early morbidity (20%) was observed at this dose.
All rats in the intraperitoneally mitoxantrone-treated group died within
the first 4 days after injection.
We conclude that controlled-release EVAc carriers deliver biologically
active mitoxantrone in a sustained fashion.
In vivo biopolymer-mediated mitoxantrone in loco chemotherapy
can significantly prolong survival in rats with intracerebral 9L gliomas.
Morbidity is mainly dose related, and can be reduced at acceptable levels
without compromising the therapeutic effect.
Keywords: brain tumor, chemotherapy, glioma, 9L, mitoxantrone, rat
Copyright
©
2004 Kluwer Academic Publishers.
All rights reserved
Source: http://ipsapp009.kluweronline.com/IPS/content/ext/x/J/5042/I/119/A/6/abstract.htm
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