Convection-enhanced delivery (CED) for the treatment of
malignant gliomas is a technique that can deliver chemotherapeutic agents directly into the
tumor and the surrounding interstitium through sustained, low-grade positive-pressure infusion. This allows for high local concentrations of drug within the
tumor while minimizing systemic levels that often lead to dose-limiting toxicity. Diffuse intrinsic pontine
gliomas (DIPGs) are universally fatal childhood
tumors for which there is currently no effective treatment. In this report the authors describe CED of the
topoisomerase inhibitor topotecan for the treatment of
DIPG in 2 children. As part of a pilot feasibility study, the authors treated 2 pediatric patients with
DIPG. Stereotactic biopsy with frozen section confirmation of glial
tumor was followed by placement of bilateral
catheters for CED of
topotecan during the same procedure. The first patient underwent CED 210 days after initial diagnosis, after
radiation therapy and at the time of
tumor recurrence, with a total dose of 0.403 mg in 6.04 ml over 100 hours. Her Karnofsky Performance Status (KPS) score was 60 before CED and 50 posttreatment. Serial MRI initially demonstrated a modest reduction in
tumor size and
edema, but the
tumor progressed and the patient died 49 days
after treatment. The second patient was treated 24 days after the initial diagnosis prior to radiation with a total dose of 0.284 mg in 5.30 ml over 100 hours. Her KPS score was 70 before CED and 50 posttreatment. Serial MRI similarly demonstrated an initial modest reduction in
tumor size. The patient subsequently underwent fractionated
radiation therapy, but the
tumor progressed and she died 120 days
after treatment.
Topotecan delivered by prolonged CED into the brainstem in children with
DIPG is technically feasible. In both patients, high infusion rates (> 0.12 ml/hr) and high infusion volumes (> 2.8 ml) resulted in new neurological deficits and reduction in the KPS score, but lower infusion rates (< 0.04 ml/hr) were well tolerated. While serial MRI showed moderate treatment effect, CED did not prolong survival in these 2 patients. More studies are needed to improve patient selection and determine the optimal flow rates for CED of chemotherapeutic agents into
DIPG to maximize safety and efficacy. Clinical trial registration no.: NCT00324844.