Treatment > Toxin Therapy

Meeting Abstract

Intratumoral infusion of IL13-PE38QQR cytotoxin for recurrent supratentorial malignant glioma: phase I/II study

Jon Weingart, Lewis Strauss, Stuart A Grossman, James Markert, Stephen Tatter, Joy D Fisher, Christina Fleming, Raj Puri

Johns Hopkins Hospital, Baltimore, MD; NeoPharm, Chicago, IL; NABTT CNS Consortium, Baltimore, MD; University of Alabama, Birmingham, AL; Wake Forest University, Winston-Salem, NC; CBER/FDA, Washington, DC

Malignant glioma cells express high-density IL-13 receptors, providing a potential target for tumor-directed cancer therapy.
IL13-PE38QQR is a recombinant protein consisting of human IL-13 and truncated form of Pseudomonas exotoxin A lacking the native binding domain.
Binding of IL13-PE38QQR to IL-13 receptor permits internalization of cytotoxin, killing tumor cells at low concentrations.
Eligibility criteria for this Phase I/II study require a prior diagnosis of supratentorial malignant glioma, recurrence after RT, measurable disease (1 to 5 cm in diameter), and a stereotaxic biopsy confirming malignant glioma at study entry.
IL13-PE38QQR is administered by microinfusion via two intratumoral catheters at 200 mL/catheter/hour for 96 hours (total 38.4 mL).
Each patient is to receive a maximum of two local cytotoxin infusions eight weeks apart.
The IL13-PE38QQR concentration is increased in each cohort of 3 patients to determine the MTD.
Cohorts are expanded to 6 patients if one DLT is observed.
Six patients have received IL13-PE38QQR at the initial dose level (concentration of 0.125 mg/mL providing a total dose of 4.8 mg/course).
One patient developed increased peritumoral edema shortly after the first infusion that responded rapidly to additional corticosteroids.
No other DLTs were observed.
A second infusion at week 9 has been given to three patients and has been well tolerated.
A radiographic response was noted in one patient 9 weeks after the initial infusion.
This patient did not receive a second infusion as the tumor shrinkage made it difficult to determine where to insert the infusion catheters.
A second patient who developed progressive neurologic findings and increased contrast enhancement underwent debulking surgery.
Pathology of the resected tissue is reported as showing only necrosis.
Three of the treated patients had disease progression at 14, 16, and 17 weeks.
The first dose escalation cohort has been associated with acceptable toxicity and a suggestion of efficacy.
Further dose escalation is planned to determine the maximum tolerated dose that will be used to formally evaluate efficacy in the Phase II portion of this study.

© Copyright 2002 American Society of Clinical Oncology