Regression of recurrent malignant gliomas with convection-enhanced delivery of topotecan

Neurosurgery. 2011 Dec;69(6):1272-9; discussion 1279-80. doi: 10.1227/NEU.0b013e3182233e24.


Background: Convection-enhanced delivery of chemotherapeutics for the treatment of malignant glioma is a technique that delivers drugs directly into a tumor and the surrounding interstitium through continuous, low-grade positive-pressure infusion. This allows high local concentrations of drug while overcoming the limitations imposed by toxicity and the blood-brain barrier in systemic therapies that prevent the use of many potentially effective drugs.

Objective: To examine the safety profile of a conventional chemotherapeutic agent, topotecan, via convection-enhanced delivery in the treatment of recurrent malignant gliomas and secondarily to assess radiographic response and survival.

Methods: We performed a prospective, dose-escalation phase Ib study of the topoisomerase-I inhibitor topotecan given by convection-enhanced delivery in patients with recurrent malignant gliomas.

Results: Significant antitumor activity as described by radiographic changes and prolonged overall survival with minimal drug-associated toxicity was demonstrated. A maximum tolerated dose was established for future phase II studies.

Conclusion: Topotecan by convection-enhanced delivery has significant antitumor activity at concentrations that are nontoxic to normal brain. The potential for use of this therapy as a generally effective treatment option for malignant gliomas will be tested in subsequent phase II and III trials.

MeSH terms

  • Adult
  • Aged
  • Attention / drug effects
  • Convection
  • Drug Administration Schedule
  • Drug Delivery Systems / methods*
  • Female
  • Follow-Up Studies
  • Glioma / diagnostic imaging
  • Glioma / drug therapy*
  • Glioma / pathology
  • Glioma / psychology
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Memory / drug effects
  • Middle Aged
  • Neurologic Examination
  • Neuropsychological Tests
  • Prospective Studies
  • Quality of Life
  • Reaction Time / drug effects
  • Supratentorial Neoplasms / diagnostic imaging
  • Supratentorial Neoplasms / drug therapy*
  • Supratentorial Neoplasms / pathology
  • Supratentorial Neoplasms / psychology
  • Surveys and Questionnaires
  • Tomography, X-Ray Computed
  • Topoisomerase I Inhibitors / administration & dosage*
  • Topotecan / administration & dosage*
  • Young Adult


  • Topoisomerase I Inhibitors
  • Topotecan