Convection-enhanced delivery of targeted toxins for malignant glioma

2006 ◽  
Vol 3 (3) ◽  
pp. 371-377 ◽  
Author(s):  
Walter A Hall ◽  
Gregory T Sherr
Keyword(s):  
Malignant Glioma ◽  
Convection Enhanced Delivery ◽  
Targeted Toxins

Direct Intracerebral Delivery of Cintredekin Besudotox (IL13-PE38QQR) in Recurrent Malignant Glioma: A Report by the Cintredekin Besudotox Intraparenchymal Study Group

2007 ◽  
Vol 25 (7) ◽  
pp. 837-844 ◽  
Author(s):  
Sandeep Kunwar ◽  
Michael D. Prados ◽  
Susan M. Chang ◽  
Mitchel S. Berger ◽  
Frederick F. Lang ◽  
...  
Keyword(s):  
Malignant Glioma ◽  
Median Survival ◽  
Tumor Resection ◽  
Drug Distribution ◽  
Catheter Placement ◽  
Recurrent Malignant Glioma ◽  
Convection Enhanced Delivery ◽  
Optimal Drug ◽  
Administration Method ◽  
Second Procedure

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 μg/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.

scholarly journals Non-PEGylated liposomes for convection-enhanced delivery of topotecan and gadodiamide in malignant glioma: initial experience

2009 ◽  
Vol 95 (2) ◽  
pp. 185-197 ◽  
Author(s):  
Amy Y. Grahn ◽  
Krystof S. Bankiewicz ◽  
Millicent Dugich-Djordjevic ◽  
John R. Bringas ◽  
Piotr Hadaczek ◽  
...  
Keyword(s):  
Malignant Glioma ◽  
Initial Experience ◽  
Convection Enhanced Delivery ◽  
Pegylated Liposomes

scholarly journals ATIM-18. PHASE I DOSE ESCALATION STUDY OF D2C7-IT ADMINISTERED INTRATUMORALLY VIA CONVECTION-ENHANCED DELIVERY (CED) FOR RECURRENT MALIGNANT GLIOMA (MG)

2016 ◽  
Vol 18 (suppl_6) ◽  
pp. vi21-vi22 ◽  
Author(s):  
Annick Desjardins ◽  
Dina Randazzo ◽  
Vidya Chandramohan ◽  
John Sampson ◽  
Katherine Peters ◽  
...  
Keyword(s):  
Phase I ◽  
Malignant Glioma ◽  
Dose Escalation ◽  
Recurrent Malignant Glioma ◽  
Convection Enhanced Delivery ◽  
Dose Escalation Study

scholarly journals ATIM-36. DOSE ESCALATION TRIAL OF D2C7 IMMUNOTOXIN (D2C7-IT) ADMINISTERED INTRATUMORALLY VIA CONVECTION-ENHANCED DELIVERY (CED) FOR RECURRENT MALIGNANT GLIOMA (MG)

2018 ◽  
Vol 20 (suppl_6) ◽  
pp. vi9-vi9 ◽  
Author(s):  
Annick Desjardins ◽  
Dina Randazzo ◽  
Vidya Chandramohan ◽  
Katherine Peters ◽  
Margaret Johnson ◽  
...  
Keyword(s):  
Malignant Glioma ◽  
Dose Escalation ◽  
Recurrent Malignant Glioma ◽  
Convection Enhanced Delivery

Convection-enhanced Delivery of Interleukin-13 Receptor-directed Cytotoxin for Malignant Glioma Therapy*

2006 ◽  
Vol 5 (3) ◽  
pp. 239-250 ◽  
Author(s):  
Mitomu Kioi ◽  
Syed R. Husain ◽  
David Croteau ◽  
Sandeep Kunwar ◽  
Raj K. Puri
Keyword(s):  
Malignant Glioma ◽  
Convection Enhanced Delivery ◽  
Interleukin 13

Neuroradiographic changes following convection-enhanced delivery of the recombinant cytotoxin interleukin 13—PE38QQR for recurrent malignant glioma

2005 ◽  
Vol 102 (2) ◽  
pp. 267-275 ◽  
Author(s):  
Ian F. Parney ◽  
Sandeep Kunwar ◽  
Michael McDermott ◽  
Mitchel Berger ◽  
Michael Prados ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Malignant Glioma ◽  
Tumor Resection ◽  
Therapeutic Agents ◽  
Grading System ◽  
Recurrent Malignant Glioma ◽  
Mr Images ◽  
Convection Enhanced Delivery ◽  
Content Type ◽  
Fine Print

Object. Convection-enhanced delivery (CED) is a novel method for delivering therapeutic agents to infiltrative brain tumor cells. For agents administered by CED, changes on magnetic resonance (MR) imaging directly resulting from catheter placement, infusion, and the therapeutic compound may confound any interpretation of tumor progression. As part of an ongoing multiinstitutional Phase I study, 14 patients with recurrent malignant glioma underwent CED of interleukin (IL) 13—PE38QQR, a recombinant cytotoxin consisting of human IL-13 conjugated with a truncated Pseudomonas exotoxin. Serial neuroradiographic changes were assessed in this cohort of patients. Methods. Patients were treated in two groups: Group 1 patients received IL13—PE38QQR before and after tumor resection; Group 2 patients received infusion only after tumor resection. Preoperative and postinfusion MR images were obtained prospectively at specified regular intervals. Changes were noted along catheter tracks on postresection MR images obtained in all patients. A simple grading system was developed to describe these changes. When MR imaging changes appeared to be related to IL13—PE38QQR, patients were followed up without instituting new antitumor therapy. Conclusions. As CED of therapeutic agents becomes more common, clinicians and investigators must become aware of associated neuroimaging changes that should be incorporated into toxicity assessment. We have developed a simple grading system to facilitate communication about these changes among investigators. Biological imaging modalities that could possibly distinguish these changes from recurrent tumor should be evaluated. In this study the authors demonstrate the challenges in determining efficacy when surrogate end points such as time to tumor progression as defined by new or progressive contrast enhancement on MR imaging are used with this treatment modality.

scholarly journals STMO-04 LOCAL CONVECTION-ENHANCED DELIVERY OF CHEMOTHERAPY AS TREATMENT FOR BRAIN TUMORS

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii19-ii19
Author(s):  
Ryuta Saito ◽  
Masayuki Kanamori ◽  
Teiji Tominaga
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Malignant Glioma ◽  
Malignant Gliomas ◽  
Recurrent Malignant Glioma ◽  
Local Chemotherapy ◽  
Open Label ◽  
Convection Enhanced Delivery ◽  
Delivery Technique ◽  
Nimustine Hydrochloride

Abstract BACKGROUND Convection-enhanced delivery (CED) of therapeutic agents is a promising local delivery technique that has been extensively studied as a treatment for CNS diseases over the last 2 decades. Applying this technique to treat brain tumors, we have been working to develop novel local chemotherapy against brain tumors. In the meanwhile, clinical trial against diffuse intrinsic brain tumor aiming at Japanese “shonin” approval is recruiting patients. In this study, potential of local CED based chemotherapy against supratentorial brain tumor is discussed. METHODS Until today, we have evaluated the safety and efficacy of local CED of nimustine hydrochloride against supratentorial malignant glioma patients in the three prospective, single institute, nonrandomized, open-label studies. Among those, one study recruited the recurrent malignant glioma patients whose enhanced tumor can be surgically resected. After the resection of the tumor, CED of ACNU was performed targeting the surrounding brain. Temozolomide was also given for 5 days during this trial. RESULTS Seven patients; 4 male and 3 female, age 33–71 y.o. (median 54 y.o.), were treated in this study. Five patients suffered glioblastoma and two suffered anaplastic astrocytoma. After the treatment, all seven patients lived longer than a year; one survived three years, one survived four and a half years, and one with glioblastoma is still alive after 5 years. DISCUSSION Potential efficacy of local chemotherapy delivering nimustine hydrochloride with CED against recurrent malignant glioma was suggested. Further study is required to pave the way for this strategy against supratentorial malignant gliomas.

Safety and Feasibility of Convection-enhanced Delivery of Cotara for the Treatment of Malignant Glioma: Initial Experience in 51 Patients

Neurosurgery ◽  
2005 ◽  
Vol 56 (6) ◽  
pp. 1243-1253 ◽  
Author(s):  
Sunil J. Patel ◽  
William R. Shapiro ◽  
Douglas W. Laske ◽  
Randy L. Jensen ◽  
Anthony L. Asher ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Adverse Events ◽  
Malignant Glioma ◽  
Tumor Volume ◽  
Single Photon ◽  
Photon Emission ◽  
Recurrent Glioblastoma ◽  
Recurrent Glioblastoma Multiforme ◽  
Convection Enhanced Delivery ◽  
Administered Activity

Abstract OBJECTIVE: We report the safety and feasibility of using convection-enhanced delivery to administer Cotara (Peregrine Pharmaceuticals, Inc., Tustin, CA), a novel radioimmunotherapeutic agent, to patients with malignant glioma. METHODS: Between April 1998 and November 2002, 51 patients with histologically confirmed malignant glioma received Cotara by convection-enhanced delivery. Most patients (88%) were treated with Cotara targeting tumor volume-dependent, single or multiple administrations of activity ranging from 0.5 to 3.0 mCi/cm3 of baseline clinical target volume. Two weeks after infusion, single-photon emission computed tomographic imaging determined the spatial distribution of Cotara. Patients were followed for as long as 41 months (average follow-up, 5 mo). Safety was evaluated on the basis of incidence of procedure-related, neurological, and systemic adverse events. Feasibility was evaluated in a subset of patients on the basis of the correlation between the prescribed activity and the actual activity administered to the targeted region. RESULTS: Fifty-one patients, 37 with recurrent glioblastoma multiforme, 8 with newly diagnosed glioblastoma multiforme, and 6 with recurrent anaplastic astrocytomas, were treated. Average tumor volume was 36 ± 27.6 cm3 (range, 5–168 cm3). Of the 67 infusions, 13 (19%), 52 (78%), and 2 (3%) delivered less than 90%, 100 ± 10%, and more than 110%, respectively, of the prescribed administered activity to the targeted region. Treatment-emergent, drug-related central nervous system adverse events included brain edema (16%), hemiparesis (14%), and headache (14%). Systemic adverse events were mild. Several patients had objective responses to Cotara. CONCLUSION: The majority of Cotara infusions delivered between 90 and 110% of the prescribed administered activity to the targeted region. This method of administration has an acceptable safety profile compared with literature reports of other therapeutics delivered by convection-enhanced delivery.

Sign in / Sign up

Export Citation Format

Share Document