Treatment > Toxin Therapy

Meeting Abstract

Determination of toxicities and maximum tolerated dose (MTD) of intra-tumoral infusion of IL13-PE38QQR cytotoxin in patients with recurrent supratentorial malignant glioma: A phase I/II study

J. Weingart, J. Markert, S. Tatter, M. Rosenblum, J. Fisher, C. Fleming, J. Steinberg, R. Puri

for the NABTT CNS Consortium; Johns Hopkins Hospital, Baltimore, MD; University of Alabama, Birmingham, AL; Wake Forest University, Winston-Salem, NC; Henry Ford, Detroit, MI; NeoPharm, Inc., Lake Forest, IL; United States Food and Drug Administration, Bethesda, MD

IL13-PE38QQR is a recombinant protein consisting of human IL13 and a truncated form of Pseudomonas Exotoxin A lacking the binding domain.
Malignant glioma cells express IL13 receptors (IL13R) at high-density, providing a potential target for therapy.
Binding of IL13-PE38QQR to IL13R permits cytotoxin internalization and killing of tumor cells at nanomolar concentrations.
Convection-enhanced delivery (CED) using positive pressure infusion is a new way to deliver therapeutic agents into tumors, or adjacent to tumor resection sites, to optimize drug distribution while minimizing systemic exposure.
The primary objective of Phase I is to determine toxicities and maximum tolerated dose (MTD) of IL13-PE38QQR delivered by continuous infusion into malignant glioma.
Phase II endpoints include response rate, duration and time to response, and survival.
To enroll, patients must have supratentorial malignant glioma recurrent after radiation therapy.
IL13-PE38QQR is administered via 2 intratumoral catheters at 200 μL/catheter/hr for 96 hours (total = 38.4 mL) x 2 courses 8 weeks apart.
As of December 2002, 15 patients had received 0.125 μg/mL (n=6), 0.25 μg/mL (n=3), 0.50 μg/mL (n=3), and 1.0 μg/mL (n=3).
Age range was 31-67 years; M:F was 13:2.
Drug-related adverse events of Grade ≥ 2 include aphasia, ataxia, brain or cerebral edema, headache, hemiparesis, and stupor.
Serious adverse events include brain edema, deep vein thrombosis, heart arrest, hemiparesis, hydrocephalus, lower extremity embolus, motor neuropathy, pneumocephaly, and thrombosis.
Three 0.125 μg/mL patients, one 0.50 μg/mL patient, and one 1.0 μg/mL patient received 2 infusions.
One patient (0.125 μg/mL) had a near complete radiographic response and 2 patients (one at 0.125 μg/mL; one at 0.50 μg/mL) had complete histopathologic responses.
Time to progression and survival are 7-46+ weeks and 10-104+ weeks, respectively.
The MTD has not been reached.
Intratumoral infusion of IL13-PE38QQR appears to be well tolerated in this population, permitting dose escalation and patient accrual to proceed.

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