Scientific Publications by FDA Staff
J Clin Oncol 2007 Mar 1;25(7):837-44
Direct intracerebral delivery of cintredekin besudotox (IL13-PE38QQR) in recurrent malignant glioma: a report by the Cintredekin Besudotox Intraparenchymal Study Group.
Kunwar S, Prados MD, Chang SM, Berger MS, Lang FF, Piepmeier JM, Sampson JH, Ram Z, Gutin PH, Gibbons RD, Aldape KD, Croteau DJ, Sherman JW, Puri RK; Cintredekin Besudotox Intraparenchymal Study Group
Kunwar S (reprint author), Univ Calif San Francisco, Dept Neurol Surg, 400 Parnassus Ave,A808, San Francisco, CA 94143 USA Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA Yale Univ, New Haven, CT USA Duke Univ, Durham, NC USA Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA Univ Illinois, Chicago, IL USA NeoPharm Inc, Waukegan, IL USA US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA Tel Aviv Univ, IL-69978 Tel Aviv, Israel
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.
|Category: Journal Article|
|PubMed ID: #17327604|
|Includes FDA Authors from Scientific Area(s): Biologics|
|Entry Created: 2011-10-04||Entry Last Modified: 2012-08-29|