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

J Clin Oncol. 2007 Mar 1;25(7):837-44. doi: 10.1200/JCO.2006.08.1117.


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.

Publication types

  • Clinical Trial, Phase I

MeSH terms

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


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