title: Efficacy of interstitial continuous vincristine infusion in a bioluminescent rodent intracranial tumor model.
abstract: Interstitial chemotherapeutic drug infusion can bypass the blood-brain barrier, and provide high regional drug concentrations without systemic exposure. However, toxicity and efficacy for drugs administered via interstitial continuous (i.c.) infusion have not been characterized. In the current study, vincristine (VIN) was infused into the right frontal lobes of healthy Fisher 344 rats at 30, 45, 60, and 120 μg/ml over a period of 7 days at 1 μl/h, using an Alzet osmotic pump to evaluate toxicity. C6 rat glioblastoma cells transduced with a luciferase gene were inoculated into the right frontal lobe of a second group of rats. VIN was administered to tumor bearing rats via i.c. infusion 7 days later and tumor growth was monitored by bioluminescence intensity (BLI) to assess VIN efficacy, intravenous (i.v.) drug administration was used as a comparison drug delivery method. The results suggested that VIN toxicity is dose-dependent. Efficacy studies showed increased BLI, which correlates with histopathological tumor size, in saline-infused and i.v.-treated tumor-bearing rats. These rats survived an average of 28 ± 0.85 days and 33 ± 1.38 days, respectively. Both groups had large tumors at the time of death. Animals treated with VIN via i.c. infusion survived until day 90, the observation endpoint for this study. This was significantly longer than average survival times in the previous two groups. These results demonstrate that VIN via i.c. infusion is effective in reducing C6 glioblastoma tumors and prolonging rodent survival time compared to i.v. injection and suggest that chemotherapeutic drug administration via i.c. infusion may be a promising strategy for treating malignant brain tumors.
authors.affiliation: Neurosurgical Department, Children's Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. gxi@childrensmemorial.org
authors.forename: Guifa
authors.initials: G
authors.lastname: Xi
authors.forename: Barbara
authors.initials: B
authors.lastname: Mania-Farnell
authors.forename: Veena
authors.initials: V
authors.lastname: Rajaram
authors.forename: Chandra S
authors.initials: CS
authors.lastname: Mayanil
authors.forename: Marcelo B
authors.initials: MB
authors.lastname: Soares
authors.forename: Tadanori
authors.initials: T
authors.lastname: Tomita
authors.forename: Stewart
authors.initials: S
authors.lastname: Goldman
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001932:Brain Neoplasms / Q000188:drug therapy*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D057967:Infusions, Intraventricular; D008163:Luminescent Measurements; D008297:Male; D009374:Neoplasms, Experimental / Q000188:drug therapy; D051381:Rats; D011916:Rats, Inbred F344; D014750:Vincristine / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D014750:Vincristine