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Regression of Recurrent Malignant Gliomas With Convection-Enhanced Delivery of Topotecan

Bruce, Jeffrey N. MD*; Fine, Robert L. MD; Canoll, Peter MD, PhD§; Yun, Jonathan MD*; Kennedy, Benjamin C. MD*; Rosenfeld, Steven S. MD, PhD; Sands, Stephen A. PsyD; Surapaneni, Krishna MD**; Lai, Rose MD; Yanes, Candix L. RN*; Bagiella, Emilia PhD#; DeLaPaz, Robert L. MD**

doi: 10.1227/NEU.0b013e3182233e24
Research-Human-Clinical Trials

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.

*Department of Neurological Surgery

Division of Medical Oncology

§Department of Pathology

Department of Neurology

Department of Pediatric Oncology

#Department of Biostatistics, and

**Department of Radiology, Columbia University Medical Center, New York, New York

Correspondence: Jeffrey N. Bruce, MD, Neurological Institute, Room 434, 710 W 168th St, New York, NY 10032. E-mail: jnb2@columbia.edu

Received November 18, 2010

Accepted April 5, 2011

Copyright © by the Congress of Neurological Surgeons