Interstitial continuous infusion therapy in a malignant glioma model in rats.
OBJECTIVE
Local direct delivery of chemotherapeutic agents for the treatment of brain tumors is an area of focus in the development of new therapeutic paradigms. These techniques need improvement, especially in terms of drug retention in brain tissue.


METHODS
In this study, we used a rat glioma model to examine carboplatin distribution, as measured by platinum penetration, after delivery via interstitial continuous (i.c.) infusion. We also examined rat survival times in response to carboplatin and oxaliplatin. I.C. infusion, a modified version of convection-enhanced delivery (CED) for local drug delivery, uses low volume (1 microl per hour) continuous infusion directly into the tumor.


RESULTS
I.C. infusion produced a nearly 360-fold higher concentration of platinum in tumor tissue and significantly prolonged rodent survival time compared to intraperitoneal (i.p.) infusion.


CONCLUSIONS
We showed i.c. infusion allows for circumvention of the blood-brain barrier, focused drug distribution, and sustained drug delivery. This method could be a promising strategy for treating brain tumors.
Tange
Yuichi
Y
Division of Pediatric Neurosurgery, Children's Memorial Hospital, Chicago, IL 60614, USA.
Kondo
Akihide
A
Egorin
Merrill J
MJ
Mania-Farnell
Barbara
B
Daneriallis
Georgy M
GM
Nakazaki
Hiromichi
H
Sredni
Simone T
ST
Rajaram
Veena
V
Goldman
Stewart
S
Soares
Marcelo B
MB
Tomita
Tadanori
T
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016190:Carboplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002404:Catheterization; D045744:Cell Line, Tumor; D003342:Corpus Striatum / Q000187:drug effects; D004195:Disease Models, Animal; D005910:Glioma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D053208:Kaplan-Meier Estimate; D008297:Male; D009368:Neoplasm Transplantation; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics; D000077150:Oxaliplatin; D010984:Platinum / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D010984:Platinum; D016190:Carboplatin