New approach to tumor therapy for inoperable areas of the brain: chronic intraparenchymal drug delivery

J Neurooncol. 2002 Nov;60(2):151-8. doi: 10.1023/a:1020626419269.

Abstract

Because the brainstem has little functional redundancy, diffuse lesions have been regarded as inoperable. To determine whether local drug therapy can prolong survival in a rodent model of a tumor in such eloquent tissue, lethal doses of F98 and 9L tumor cells were injected into the brainstems of Fischer 344 rats. Five days after inoculations, 0.5 mg/ml solutions of carboplatin were infused at 1 microl/h for 7 days. Compared to control groups that survived 13-17 days with F98 tumors and 22-23 days with 9L tumors, animals locally infused with 0.1 mg of carboplatin survived 27-30 days (Prob > Chi Sq = 0.0003), and 32 days (Prob > Chi Sq = 0.01), respectively. Measurements of tissue platinum levels at autopsy suggested that infusions distributed pharmacologically relevant levels of carboplatin through a volume of tissue at least 0.5 cm in diameter. The results suggest that chronic low-flow infusions provide a promising approach to therapy for CNS lesions in tissues considered to be inoperable.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Brain Stem Neoplasms / drug therapy*
  • Brain Stem Neoplasms / mortality
  • Brain Stem Neoplasms / surgery
  • Carboplatin / pharmacology*
  • Drug Delivery Systems*
  • Female
  • Glioma / drug therapy*
  • Glioma / mortality
  • Glioma / surgery
  • Infusion Pumps
  • Rats
  • Rats, Inbred F344
  • Survival Analysis

Substances

  • Antineoplastic Agents
  • Carboplatin