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

Jeffrey N. Bruce, Robert L. Fine, Peter Canoll, Jonathan Yun, Benjamin C. Kennedy, Steven S. Rosenfeld, Stephen A. Sands, Krishna Surapaneni, Rose Lai, Candix L. Yanes, Emilia Bagiella, Robert L. Delapaz

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1272-1279
Number of pages8
JournalNeurosurgery
Volume69
Issue number6
DOIs
StatePublished - Dec 2011

Keywords

  • Clinical trial
  • Glioblastoma
  • Glioma
  • Topotecan

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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    Bruce, J. N., Fine, R. L., Canoll, P., Yun, J., Kennedy, B. C., Rosenfeld, S. S., Sands, S. A., Surapaneni, K., Lai, R., Yanes, C. L., Bagiella, E., & Delapaz, R. L. (2011). Regression of recurrent malignant gliomas with convection-enhanced delivery of topotecan. Neurosurgery, 69(6), 1272-1279. https://doi.org/10.1227/NEU.0b013e3182233e24