Interstitial continuous infusion therapy in a malignant glioma model in rats

Childs Nerv Syst. 2009 Jun;25(6):655-62. doi: 10.1007/s00381-008-0805-3. Epub 2009 Feb 11.

Abstract

Purpose: 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.

Materials and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacokinetics
  • Blood-Brain Barrier / drug effects
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Carboplatin / administration & dosage*
  • Carboplatin / pharmacokinetics
  • Catheterization
  • Cell Line, Tumor
  • Corpus Striatum / drug effects
  • Disease Models, Animal
  • Glioma / drug therapy*
  • Glioma / mortality
  • Glioma / pathology
  • Kaplan-Meier Estimate
  • Male
  • Neoplasm Transplantation
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / pharmacokinetics
  • Oxaliplatin
  • Platinum / metabolism
  • Rats
  • Rats, Inbred F344
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Organoplatinum Compounds
  • Oxaliplatin
  • Platinum
  • Carboplatin