Direct intracerebral delivery of cintredekin besudotox (IL13-PE38QQR) in recurrent malignant glioma: a report by the Cintredekin Besudotox Intraparenchymal Study Group.

Abstract

PURPOSE:

Glioblastoma multiforme (GBM) is a devastating brain tumor with a median survival of 6 months after recurrence. Cintredekin besudotox (CB) is a recombinant protein consisting of interleukin-13 (IL-13) and a truncated form of Pseudomonas exotoxin (PE38QQR). Convection-enhanced delivery (CED) is a locoregional-administration method leading to high-tissue concentrations with large volume of distributions. We assessed the use of intracerebral CED to deliver CB in patients with recurrent malignant glioma (MG).

PATIENTS AND METHODS:

Three phase I clinical studies evaluated intracerebral CED of CB along with tumor resection. The main objectives were to assess the tolerability of various concentrations and infusion durations; tissue distribution; and methods for optimizing delivery. All patients underwent tumor resection followed by a single intraparenchymal infusion (in addition to the intraparenchymal one following resection), with a portion of patients who had a preresection intratumoral infusion.

RESULTS:

A total of 51 patients with MG were treated including 46 patients with GBM. The maximum tolerated intraparenchymal concentration was 0.5 microg/mL and tumor necrosis was observed at this concentration. Infusion durations of up to 6 days were well tolerated. Postoperative catheter placement appears to be important for optimal drug distribution. CB- and procedure-related adverse events were primarily limited to the CNS. Overall median survival for GBM patients is 42.7 weeks and 55.6 weeks for patients with optimally positioned catheters with patient follow-up extending beyond 5 years.

CONCLUSION:

CB appears to have a favorable risk-benefit profile. CED is a complex delivery method requiring catheter placement via a second procedure to achieve accurate catheter positioning, better drug distribution, and better outcome.

• Authors: Sandeep Kunwar, Michael D Prados, Susan M Chang, Mitchel S Berger, Frederick F Lang, Joseph M Piepmeier, John H Sampson, Zvi Ram, Philip H Gutin, Robert D Gibbons, Kenneth D Aldape, David J Croteau, Jeffrey W Sherman, Raj K Puri, Cintredekin Besudotox Intraparenchymal Study Group
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 25 Issue 7 Pg. 837-44 (Mar 01 2007) ISSN: 1527-7755 [Electronic] United States
• PMID: 17327604 (Publication Type: Clinical Trial, Phase I, Journal Article)

Chemical References

• Exotoxins
• IL13-PE38
• Immunotoxins
• Interleukin-13
• Recombinant Fusion Proteins

Topics

• Adult
• Aged
• Catheterization
• Convection
• Drug Delivery Systems (methods)
• Exotoxins (administration & dosage, adverse effects, pharmacokinetics)
• Female
• Glioma (drug therapy, mortality)
• Humans
• Immunotoxins (administration & dosage)
• Interleukin-13 (administration & dosage, adverse effects, pharmacokinetics)
• Male
• Middle Aged
• Neoplasm Recurrence, Local
• Recombinant Fusion Proteins
• Supratentorial Neoplasms (drug therapy, mortality)
• Tissue Distribution