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

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

Jeffrey N Bruce  1 , 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
Affiliations

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

Jeffrey N Bruce et al. Neurosurgery. 2011 Dec.

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.

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Figures

FIGURE 1
FIGURE 1
Early response. A, each of the 4 early responding patients’ contrast-enhancing volume plotted over time. Early response refers to a decrease in contrast-enhancing volume through at least the first 3 months of therapy. B, serial contrast-enhanced T1-weighted MRI scans from the patient with the greatest response to 10 months in A showing complete resolution of contrast enhancement at 1.5 years (indistinct high signal was present on noncontrast scans) with tumor recurrence predominantly at the inferior treatment (Tx) margin at 2.5 years.
FIGURE 2
FIGURE 2
Progressive disease. A, contrast-enhancing volume of each of the 5 patients with progressive disease after therapy plotted over time. Progressive disease refers to increasing contrast-enhancing volume at ≥1 month after therapy until surgical resection or death. B, serial contrast-enhanced T1-weighted MRI scans from the patient with the greatest progression at 8 months in A showing a rapid increase in contrast enhancement and necrosis at the treatment site and inferior to the treatment (Tx) margin (surgical resection followed the last scan).
FIGURE 3
FIGURE 3
Pseudoprogression. A, each of the 7 pseudoprogressors’ contrast-enhancing volume plotted over time. Pseudoprogression refers to an increase in the contrast-enhancing volume after therapy, followed by regression of enhancement and edema, especially within the first 3 months after therapy. B, serial contrast-enhanced T1-weighted MRI scans from a patient with pseudopregression at 1 to 3 months and response at 6 to 8 months without further therapy until surgical resection of tumor recurrence at the inferior treatment (Tx) margin at 10 months. C, serial contrast-enhanced T1-weighted MRI scans from a patient with pseudoprogression at 1 month and response at 5 to 7 months without further therapy until surgical resection of tumor recurrence at 9 months.
See this image and copyright information in PMC

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