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.

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 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

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.

An inflatable balloon catheter and liquid 125I radiation source (GliaSite Radiation Therapy System) for treatment of recurrent malignant glioma: multicenter safety and feasibility trial

2003 ◽  
Vol 99 (2) ◽  
pp. 297-303 ◽  
Author(s):  
Stephen B. Tatter ◽  
Edward G. Shaw ◽  
Mark L. Rosenblum ◽  
Kastytis C. Karvelis ◽  
Lawrence Kleinberg ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Malignant Glioma ◽  
Tumor Resection ◽  
Balloon Catheter ◽  
Target Volume ◽  
Feasibility Trial ◽  
Recurrent Malignant Glioma ◽  
Content Type ◽  
And Performance ◽  
Fine Print

Object. In this study the authors evaluated the safety and performance of the GliaSite Radiation Therapy System (RTS) in patients with recurrent malignant brain tumors who were undergoing tumor resection. Methods. The GliaSite is an inflatable balloon catheter that is placed in the resection cavity at the time of tumor debulking. Low-dose-rate radiation is delivered with an aqueous solution of organically bound iodine-125 (Iotrex [sodium 3-(125I)-iodo-4-hydroxybenzenesulfonate]), which are temporarily introduced into the balloon portion of the device via a subcutaneous port. Adults with recurrent malignant glioma underwent resection and GliaSite implantation. One to 2 weeks later, the device was filled with Iotrex for 3 to 6 days, following which the device was explanted. Twenty-one patients with recurrent high-grade astrocytomas were enrolled in the study and received radiation therapy. There were two end points: 1) successful implantation and delivery of brachytherapy; and 2) safety of the device. Implantation of the device, delivery of radiation, and the explantation procedure were well tolerated. At least 40 to 60 Gy was delivered to all tissues within the target volume. There were no serious adverse device-related events during brachytherapy. One patient had a pseudomeningocele, one patient had a wound infection, and three patients had meningitis (one bacterial, one chemical, and one aseptic). No symptomatic radiation necrosis was identified during 21.8 patient-years of follow up. The median survival of previously treated patients was 12.7 months (95% confidence interval 6.9–15.3 months). Conclusions. The GliaSite RTS performs safely and efficiently. It delivers a readily quantifiable dose of radiation to tissue at the highest risk for tumor recurrence.

scholarly journals Early Cerebral Blood Volume Changes Predict Progression After Convection-Enhanced Delivery of Topotecan for Recurrent Malignant Glioma

2015 ◽  
Vol 84 (1) ◽  
pp. 163-172 ◽  
Author(s):  
Krishna Surapaneni ◽  
Benjamin C. Kennedy ◽  
Ted K. Yanagihara ◽  
Robert DeLaPaz ◽  
Jeffrey N. Bruce
Keyword(s):  
Malignant Glioma ◽  
Blood Volume ◽  
Cerebral Blood Volume ◽  
Recurrent Malignant Glioma ◽  
Volume Changes ◽  
Convection Enhanced Delivery

scholarly journals DDEL-16. UNDERSTANDING OPTIMAL CONVECTION-ENHANCED DELIVERY PHYSICO-CHEMICAL INFUSION PARAMETERS: THE ROLE OF BBB EFFLUX PUMPS IN DRUG DISTRIBUTION AND CLEARANCE

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii286-iii287
Author(s):  
Erica Power ◽  
Liang Zhang ◽  
David Daniels
Keyword(s):  
Drug Concentration ◽  
Efflux Pump ◽  
Drug Distribution ◽  
Efflux Pumps ◽  
Drug Clearance ◽  
Convection Enhanced Delivery ◽  
Efflux Pump Inhibition ◽  
Physico Chemical ◽  
Delivery Technique ◽  
Optimal Drug

Abstract BACKGROUND Diffuse midline gliomas harboring the H3K27M mutation are aggressive and universally fatal brain tumors that primarily occur in children. The blood-brain barrier (BBB) prevents many drugs from reaching the tumor at cytotoxic concentrations and efflux pumps found on the epithelial cells of the BBB rapidly pump drugs out of the brain. Convection enhanced delivery (CED) is a drug delivery technique that bypasses the BBB by directly injecting the drug into the tumor site under a pressure gradient. Further clinical implementation of CED requires understanding drug distribution, as optimal drug physico-chemical properties have never been evaluated. METHODS Sprague Dawley rats underwent a single injection of drug by CED to the brainstem with and without an efflux pump inhibitor. Animals were euthanized at 0, 2, 4, 8, 12 and 24 hours. Their brain drug concentration/distribution was analyzed by MALDI-MSI and plasma drug concentration was measured by LC-MS/MS. RESULTS Drug distribution and brainstem concentration were increased following BBB efflux pump inhibition compared to no pump inhibition controls. Additionally, efflux pump inhibition resulted in slower drug clearance for those drugs that are known pump substrates. CONCLUSIONS BBB efflux pump inhibition resulted in a larger volume of distribution, increased drug concentration and slower drug clearance following CED to the brainstem of known efflux substrates.

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