Interstitial infusion of erlotinib in the rodent brain.
A critical need exists for the development of novel forms of treatment for high-grade glioma. Molecular characterization of high-grade glioma has shown overexpression of the epidermal growth factor receptor, antagonists to which, including erlotinib, may prevent tumor growth. Interstitial infusion is a mode of local delivery which bypasses the blood-brain barrier and utilizes a pressure-dependent gradient to enhance drug uniformity and volume of distribution. Interstitial infusion of erlotinib was performed to the striatum of 12 rats in increasing, therapeutic doses. No evidence of clinical or histopathologic toxicity was found. In this experimental study we demonstrate that interstitial infusion of erlotinib is safe in the rodent brain, and may have potential applicability for the treatment of high-grade glioma.
Luther
Neal
N
Department of Neurological Surgery, Weill Medical College of Cornell University, 1300 York Ave, Box 99 New York, NY 10021, USA. nel2003@nyp.org
Karampelas
Ioannis
I
Souliopoulos
Eleni P
EP
Edgar
Mark A
MA
Boockvar
John A
JA
Souweidane
Mark M
MM
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000473:pathology / Q000502:physiology; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000069347:Erlotinib Hydrochloride; D005910:Glioma / Q000188:drug therapy / Q000473:pathology; D008845:Microinjections; D017072:Neostriatum / Q000502:physiology; D011799:Quinazolines / Q000008:administration & dosage* / Q000627:therapeutic use / Q000633:toxicity*; D051381:Rats; D011923:Rats, Nude
D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors