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Convection-enhanced delivery of cintredekin besudotox (interleukin-13-PE38QQR) followed by radiation therapy with and without temozolomide in newly diagnosed malignant gliomas: phase 1 study of final safety results.

Publication ,  Journal Article
Vogelbaum, MA; Sampson, JH; Kunwar, S; Chang, SM; Shaffrey, M; Asher, AL; Lang, FF; Croteau, D; Parker, K; Grahn, AY; Sherman, JW; Husain, SR ...
Published in: Neurosurgery
November 2007

OBJECTIVE: Cintredekin besudotox (CB), a recombinant cytotoxin consisting of interleukin-13 and truncated Pseudomonas exotoxin, binds selectively to interleukin-13R alpha2 receptors overexpressed by malignant gliomas. This study assessed the safety of CB administered by convection-enhanced delivery followed by standard external beam radiation therapy (EBRT) with or without temozolomide (Temodar; Schering-Plough, Kenilworth, NJ) in patients with newly diagnosed malignant gliomas. METHODS: After gross total resection of the tumor, two to four intraparenchymal catheters were stereotactically placed and CB (0.25 or 0.5 microg/mL) was infused for 96 hours. This was followed, 10 to 14 days later, by EBRT (5940-6100 cGy, 5 d/wk for 6-7 wk) with or without temozolomide (75 mg/m/d, 7 d/wk during EBRT). Safety was assessed during an 11-week observation period after catheter placement RESULTS: Twenty-two patients (12 men, 10 women; median age, 55 yr; 21 with glioblastoma multiforme and one with an anaplastic mixed oligoastrocytoma) were enrolled. None of the patients experienced dose-limiting toxicities in the first two cohorts (0.25 microg/mL CB + EBRT [n = 3] and 0.25 microg/mL CB + EBRT + temozolomide [n = 3]). One patient experienced a dose-limiting toxicity (Grade 4 seizure) in the third cohort (0.5 microg/mL CB + EBRT [n = 6]). Six patients in the final cohort (0.5 microg/mL CB + EBRT + temozolomide [n = 10]) completed treatment, and one patient experienced a dose-limiting toxicity (Grade 3 aphasia and confusion). Four patients were not considered evaluable for a dose decision and were replaced. CB related adverse events occurring in more than one patient were fatigue, gait disturbance, nystagmus, and confusion. No Grade 3 to 4 hematological toxicities were observed. CONCLUSION: CB (0.5 microg/mL) administered via convection-enhanced delivery before standard radiochemotherapy seems to be well tolerated in adults with newly diagnosed malignant gliomas. Further clinical study assessment is warranted.

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Published In

Neurosurgery

DOI

EISSN

1524-4040

Publication Date

November 2007

Volume

61

Issue

5

Start / End Page

1031 / 1037

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Temozolomide
  • Recombinant Fusion Proteins
  • Radiotherapy, Conformal
  • Neurology & Neurosurgery
  • Nervous System Diseases
  • Middle Aged
  • Male
  • Interleukin-13
  • Infusions, Intralesional
 

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Vogelbaum, M. A., Sampson, J. H., Kunwar, S., Chang, S. M., Shaffrey, M., Asher, A. L., … Puri, R. K. (2007). Convection-enhanced delivery of cintredekin besudotox (interleukin-13-PE38QQR) followed by radiation therapy with and without temozolomide in newly diagnosed malignant gliomas: phase 1 study of final safety results. Neurosurgery, 61(5), 1031–1037. https://doi.org/10.1227/01.neu.0000303199.77370.9e
Vogelbaum, Michael A., John H. Sampson, Sandeep Kunwar, Susan M. Chang, Mark Shaffrey, Anthony L. Asher, Frederick F. Lang, et al. “Convection-enhanced delivery of cintredekin besudotox (interleukin-13-PE38QQR) followed by radiation therapy with and without temozolomide in newly diagnosed malignant gliomas: phase 1 study of final safety results.Neurosurgery 61, no. 5 (November 2007): 1031–37. https://doi.org/10.1227/01.neu.0000303199.77370.9e.
Vogelbaum MA, Sampson JH, Kunwar S, Chang SM, Shaffrey M, Asher AL, Lang FF, Croteau D, Parker K, Grahn AY, Sherman JW, Husain SR, Puri RK. Convection-enhanced delivery of cintredekin besudotox (interleukin-13-PE38QQR) followed by radiation therapy with and without temozolomide in newly diagnosed malignant gliomas: phase 1 study of final safety results. Neurosurgery. 2007 Nov;61(5):1031–1037.
Journal cover image

Published In

Neurosurgery

DOI

EISSN

1524-4040

Publication Date

November 2007

Volume

61

Issue

5

Start / End Page

1031 / 1037

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Temozolomide
  • Recombinant Fusion Proteins
  • Radiotherapy, Conformal
  • Neurology & Neurosurgery
  • Nervous System Diseases
  • Middle Aged
  • Male
  • Interleukin-13
  • Infusions, Intralesional