Journal of Clinical Oncology, 2005 ASCO Annual Meeting Proceedings.
Vol 23, No 16S (June 1 Supplement), 2005: 1506
© 2005 American Society of Clinical Oncology

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Abstract

Final results of phase I/II studies of IL13-PE38QQR administered intratumorally (IT) and/or peritumorally (PT) via convection-enhanced delivery (CED) in patients undergoing tumor resection for recurrent malignant glioma

Univ of CA, San Francisco, CA; M.D. Anderson Cancer Ctr, Houston, TX; Tel Aviv Univ, Tel Aviv, Israel; Univ Hosp Hamburg-Eppendorf, Hamburg, Germany; The Cleveland Cinic Fdn, Cleveland, OH; Duke Univ Medcl Ctr, Durham, NC; NeoPharm, Inc., Lake Forest, IL; CBER U. S. FDA, Bethesda, MD

1506

Background: IL13-PE38QQR (IL13PE) is a recombinant cytotoxin which binds selectively to the IL13 receptor that is over-expressed on malignant glioma cells. CED utilizes positive pressure infusion to achieve loco-regional delivery of therapeutic agents via intracerebral catheters. Given the infiltrative nature of malignant glioma, two approaches were examined in three Phase I/II studies. Methods: IL13PE was infused IT before resection, and/or PT after resection. Safety and tolerability of IL13PE, different dosing regimens, catheter positioning, and efficacy as measured by overall survival (OS) were evaluated. The distribution of an imaging tracer co-infused with IL13PE was also assessed by SPECT. Results: Enrollment is complete; 74 adult patients received IL13PE. Dose-limiting toxicity consisted of non-specific necrosis of tumor-infiltrated and normal brain parenchyma which occurred at 1.0 µg/mL with PT administration. The maximum tolerated dose for PT infusions was 0.5 µg/mL. Higher concentrations (up to 3 µg/mL) were tolerated in the IT setting. The most common drug related adverse events were headache (31%), hemiparesis (16%), and fatigue (11%). SPECT imaging showed that distribution was confined to the solid tumor with IT infusion, but distribution to parenchyma at risk for tumor infiltration could be achieved with PT infusion. Improved OS was observed in patients with glioblastoma multiforme (GBM) receiving PT infusions (45.9 wks, n=45) as compared to patients given IT infusion (37.1 wks, n=22). In the PT setting, OS was 70.3 weeks (n=26) for patients with 2 optimally placed catheters compared to 41.4 weeks (n=19) for those with <2 optimally placed catheters. Deferred catheter placement led to a greater percentage of optimally placed catheters. Conclusions: CED of IL13PE has a favorable risk/benefit profile for treatment of patients with GBM undergoing tumor resection. Based on these results, the design of the ongoing Phase III study incorporates deferred catheter placement and PT infusion of 0.5 µg/mL of IL13PE.

Author Disclosure

Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration NeoPharm

Abstract presentation from the 2005 ASCO Annual Meeting