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Safety of intraparenchymal convection-enhanced delivery of cintredekin besudotox in early-phase studies.

Publication ,  Journal Article
Kunwar, S; Chang, SM; Prados, MD; Berger, MS; Sampson, JH; Croteau, D; Sherman, JW; Grahn, AY; Shu, VS; Dul, JL; Husain, SR; Joshi, BH ...
Published in: Neurosurg Focus
April 15, 2006

OBJECT: Convection-enhanced delivery (CED) is an increasingly used novel local/regional delivery method targeted directly to tissue. It relies on a continuous pressure gradient for distribution of therapeutic agents into the interstitial space, with administration of the infusate over a few days. Cintredekin besudotox (also known as IL13- PE38QQR) is a recombinant chimeric cytotoxin consisting of interleukin-13 and a truncated exotoxin produced by the Pseudomonas aeruginosa bacterium, which targets malignant glioma cells. METHODS: Cintredekin besudotox was administered via intraparenchymal CED after resection of supratentorial recurrent malignant glioma. The safety and toxicity profile was reviewed for 53 patients in whom infusion catheters had been placed; 51 of them received CED of the study drug. Adverse events were categorized based on time of onset in relation to CED, and the causal relationship with catheter placement or delivery of cintredekin besudotox. Catheters were placed in 53 patients, although only 51 of them received cintredekin besudotox. Most adverse events related to catheter placement or the study drug originated from the central nervous system. Three symptomatic windows were defined: the first one was between surgical procedure and CED; the second was during CED and up to 1 week after its completion; and the third window was 2 to 10 weeks after treatment. Those windows generally reflected adverse events related to surgical procedures, mass effect from infusate, and drug effect on tumor-infiltrated and normal brain parenchyma, respectively. CONCLUSIONS: The symptomatic windows identified in this study apply to any CED clinical trials, particularly those in which chimeric cytotoxins are used, and will help to determine the most likely underlying pathophysiological process causing symptoms. This information, in turn, will help to prevent adverse events or minimize their severity. Those events also have implications for dose escalation and outcome measures.

Duke Scholars

Published In

Neurosurg Focus

EISSN

1092-0684

Publication Date

April 15, 2006

Volume

20

Issue

4

Start / End Page

E15

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Recombinant Fusion Proteins
  • Pseudomonas aeruginosa
  • Postoperative Complications
  • Neurology & Neurosurgery
  • Middle Aged
  • Male
  • Magnetic Resonance Imaging
  • Interleukin-13
  • Infusion Pumps
 

Citation

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MLA
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Kunwar, S., Chang, S. M., Prados, M. D., Berger, M. S., Sampson, J. H., Croteau, D., … Puri, R. K. (2006). Safety of intraparenchymal convection-enhanced delivery of cintredekin besudotox in early-phase studies. Neurosurg Focus, 20(4), E15.
Kunwar, Sandeep, Susan M. Chang, Michael D. Prados, Mitchel S. Berger, John H. Sampson, David Croteau, Jeffrey W. Sherman, et al. “Safety of intraparenchymal convection-enhanced delivery of cintredekin besudotox in early-phase studies.Neurosurg Focus 20, no. 4 (April 15, 2006): E15.
Kunwar S, Chang SM, Prados MD, Berger MS, Sampson JH, Croteau D, et al. Safety of intraparenchymal convection-enhanced delivery of cintredekin besudotox in early-phase studies. Neurosurg Focus. 2006 Apr 15;20(4):E15.
Kunwar, Sandeep, et al. “Safety of intraparenchymal convection-enhanced delivery of cintredekin besudotox in early-phase studies.Neurosurg Focus, vol. 20, no. 4, Apr. 2006, p. E15.
Kunwar S, Chang SM, Prados MD, Berger MS, Sampson JH, Croteau D, Sherman JW, Grahn AY, Shu VS, Dul JL, Husain SR, Joshi BH, Pedain C, Puri RK. Safety of intraparenchymal convection-enhanced delivery of cintredekin besudotox in early-phase studies. Neurosurg Focus. 2006 Apr 15;20(4):E15.

Published In

Neurosurg Focus

EISSN

1092-0684

Publication Date

April 15, 2006

Volume

20

Issue

4

Start / End Page

E15

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Recombinant Fusion Proteins
  • Pseudomonas aeruginosa
  • Postoperative Complications
  • Neurology & Neurosurgery
  • Middle Aged
  • Male
  • Magnetic Resonance Imaging
  • Interleukin-13
  • Infusion Pumps