Thema: News: Pre- and post-operative infusion of IL13-PE38QQR cytotoxin
News: Pre- and post-operative infusion of IL13-PE38QQR cytotoxin
Katja[a]
29.06.2003 23:54:07
39th ASCO Annual Meeting . Chicago, IL . May 31-June 3, 2003
(Abstract No. 476)
Pre- and post-operative infusion of IL13-PE38QQR cytotoxin by convection-enhanced delivery (CED) in recurrent malignant glioma: A phase I study
S. Kunwar, M. Prados, F. Lang, C. Fleming, K. Aldape, P. Gutin, J. Raizer, J. Piepmeier, M. Berger, R. Puri
University of California at San Francisco, San Francisco, CA; M.D. Anderson Cancer Center, Houston, TX; NeoPharm, Inc., Lake Forest, IL; Memorial Sloan-Kettering Cancer Center, New York, NY; Yale University School of Medicine, New Haven, CT; United States Food and Drug Administration, Bethesda, MD
IL13-PE38QQR, a recombinant tumor-targeted cytotoxin, combines the enzymatically-active portions of Pseudomonas Exotoxin A with human IL13.
Binding of IL13-PE38QQR to IL13R permits cytotoxin internalization and killing of tumor cells at nanomolar concentrations. Normal brain tissue expresses little or no IL13R, but malignant gliomas overexpress IL13R.
Convection-enhanced delivery (CED) using positive pressure infusion is a new approach to delivering therapeutic agents into tumors, or adjacent to tumor resection sites, to optimize drug distribution while minimizing systemic exposure. Primary objectives of this study include determination of histologically effective concentration (HEC) and the corresponding drug toxicities following IL13-PE38QQR infusion.
Secondary objectives are the determination of time to progression and survival.
In Stage 1, patients receive drug intratumorally before (escalating concentrations) and peritumorally after (0.25 μg/mL, fixed) resection.
On Day 8 of Stage 1, en bloc resection is performed to assess HEC and 2-3 peritumoral catheters are placed adjacent to the resection site.
In Stage 2, the pre-resection infusion is eliminated and post-resection drug concentrations are escalated.
Age range: 24-69 years; M:F = 11:10.
In Stage 1, 15 patients were treated at escalating pre-resection concentrations (0.25, 0.50, 1.0, and 2.0 μg/mL).
Escalation of post-resection infusions has begun at 0.50 μg/mL (n=6).
The most common related adverse event (Grade ³ 2) has been headache.
Nine patients have reported serious adverse events of craniotomy flap edema, CSF drainage, CSF leakage, dehydration, expressive dysphagia, hemiparesis, meningitis, pneumocephalus, pulmonary embolus, seizure, and thrombosis.
These events have not precluded dose escalation.
Evidence of drug-induced tumor necrosis at 0.50, 1.0, and 2.0 μg/mL was observed, with 5 patients demonstrating necrosis in a zone up to 2.5 cm from the catheter.
As of December 2002, time to progression and survival are 1+-77+ weeks and 1+-77+ weeks, respectively.
Patient accrual continues in Stage 2.
© Copyright 2003 American Society of Clinical Oncology All rights reserved worldwide
(Abstract No. 476)
Pre- and post-operative infusion of IL13-PE38QQR cytotoxin by convection-enhanced delivery (CED) in recurrent malignant glioma: A phase I study
S. Kunwar, M. Prados, F. Lang, C. Fleming, K. Aldape, P. Gutin, J. Raizer, J. Piepmeier, M. Berger, R. Puri
University of California at San Francisco, San Francisco, CA; M.D. Anderson Cancer Center, Houston, TX; NeoPharm, Inc., Lake Forest, IL; Memorial Sloan-Kettering Cancer Center, New York, NY; Yale University School of Medicine, New Haven, CT; United States Food and Drug Administration, Bethesda, MD
IL13-PE38QQR, a recombinant tumor-targeted cytotoxin, combines the enzymatically-active portions of Pseudomonas Exotoxin A with human IL13.
Binding of IL13-PE38QQR to IL13R permits cytotoxin internalization and killing of tumor cells at nanomolar concentrations. Normal brain tissue expresses little or no IL13R, but malignant gliomas overexpress IL13R.
Convection-enhanced delivery (CED) using positive pressure infusion is a new approach to delivering therapeutic agents into tumors, or adjacent to tumor resection sites, to optimize drug distribution while minimizing systemic exposure. Primary objectives of this study include determination of histologically effective concentration (HEC) and the corresponding drug toxicities following IL13-PE38QQR infusion.
Secondary objectives are the determination of time to progression and survival.
In Stage 1, patients receive drug intratumorally before (escalating concentrations) and peritumorally after (0.25 μg/mL, fixed) resection.
On Day 8 of Stage 1, en bloc resection is performed to assess HEC and 2-3 peritumoral catheters are placed adjacent to the resection site.
In Stage 2, the pre-resection infusion is eliminated and post-resection drug concentrations are escalated.
Age range: 24-69 years; M:F = 11:10.
In Stage 1, 15 patients were treated at escalating pre-resection concentrations (0.25, 0.50, 1.0, and 2.0 μg/mL).
Escalation of post-resection infusions has begun at 0.50 μg/mL (n=6).
The most common related adverse event (Grade ³ 2) has been headache.
Nine patients have reported serious adverse events of craniotomy flap edema, CSF drainage, CSF leakage, dehydration, expressive dysphagia, hemiparesis, meningitis, pneumocephalus, pulmonary embolus, seizure, and thrombosis.
These events have not precluded dose escalation.
Evidence of drug-induced tumor necrosis at 0.50, 1.0, and 2.0 μg/mL was observed, with 5 patients demonstrating necrosis in a zone up to 2.5 cm from the catheter.
As of December 2002, time to progression and survival are 1+-77+ weeks and 1+-77+ weeks, respectively.
Patient accrual continues in Stage 2.
© Copyright 2003 American Society of Clinical Oncology All rights reserved worldwide
Katja[a]
