Specific therapy for high-grade glioma by convection-enhanced delivery of the TGF-β2 specific antisense oligonucleotide AP 12009

2004 ◽  
Vol 22 (14_suppl) ◽  
pp. 1514-1514 ◽  
Author(s):  
U. Bogdahn ◽  
P. Hau ◽  
A. Brawanski ◽  
J. Schlaier ◽  
M. Mehdorn ◽  
...  
Keyword(s):  
Antisense Oligonucleotide ◽  
High Grade Glioma ◽  
High Grade ◽  
Convection Enhanced Delivery ◽  
Specific Therapy

Specific therapy for high-grade glioma by convection-enhanced delivery of the TGF-β2 specific antisense oligonucleotide AP 12009

2004 ◽  
Vol 22 (14_suppl) ◽  
pp. 1514-1514 ◽  
Author(s):  
U. Bogdahn ◽  
P. Hau ◽  
A. Brawanski ◽  
J. Schlaier ◽  
M. Mehdorn ◽  
...  
Keyword(s):  
Antisense Oligonucleotide ◽  
High Grade Glioma ◽  
High Grade ◽  
Convection Enhanced Delivery ◽  
Specific Therapy

scholarly journals Convection Enhanced Delivery in the Setting of High-Grade Gliomas

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 561
Author(s):  
Chibueze D. Nwagwu ◽  
Amanda V. Immidisetti ◽  
Michael Y. Jiang ◽  
Oluwasegun Adeagbo ◽  
David C. Adamson ◽  
...  
Keyword(s):  
Rapid Development ◽  
Systemic Exposure ◽  
Therapeutic Index ◽  
High Grade Glioma ◽  
High Grade ◽  
Clinical Experiences ◽  
Convection Enhanced Delivery ◽  
Drug Concentrations ◽  
Infiltrative Growth Pattern ◽  
High Grade Gliomas

Development of effective treatments for high-grade glioma (HGG) is hampered by (1) the blood–brain barrier (BBB), (2) an infiltrative growth pattern, (3) rapid development of therapeutic resistance, and, in many cases, (4) dose-limiting toxicity due to systemic exposure. Convection-enhanced delivery (CED) has the potential to significantly limit systemic toxicity and increase therapeutic index by directly delivering homogenous drug concentrations to the site of disease. In this review, we present clinical experiences and preclinical developments of CED in the setting of high-grade gliomas.

CTNI-41. INITIAL RESULTS OF A PHASE I WINDOW OF OPPORTUNITY TRIAL EVALUATING A FIRST-IN-CLASS CD29 INHIBITOR, OS2966, IN RECURRENT HIGH-GRADE GLIOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi69-vi69
Author(s):  
James Liu ◽  
Chibueze D Nwagwu ◽  
Amanda V Immidisetti ◽  
Gabriela Bukanowska ◽  
Anne-Marie Carbonell ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase I ◽  
Tumor Resection ◽  
High Grade Glioma ◽  
Underlying Disease ◽  
Tissue Level ◽  
High Grade ◽  
Convection Enhanced Delivery ◽  
Tumor Biopsy ◽  
Safety Issues

Abstract BACKGROUND OS2966 is a first-in-class, humanized and deimmunized monoclonal antibody which antagonizes CD29/β1integrin, a mechanosignaling receptor prominently upregulated in glioblastoma. Preclinical studies in mice and non-human primates have demonstrated safety and encouraging efficacy. A two-part, ascending concentration, phase I clinical trial was therefore initiated to evaluate the safety and feasibility of delivering OS2966 directly to the site of disease via convection-enhanced delivery (CED) in recurrent high-grade glioma patients. METHODS This study has a 2-part design: In part 1, patients undergo stereotactic tumor biopsy followed by placement of a multiport CED catheter for delivery of OS2966 to the bulk contrast enhancing tumor. Subsequently, patients undergo a clinically-indicated tumor resection followed by placement of two CED catheters and delivery of OS2966 to the surrounding tumor-infiltrated brain. A unique concentration-based accelerated titration design is utilized for dose escalation. Given availability of pre and post infusion samples, pharmacodynamic data will be analyzed to explore mechanism of action of OS2966. RESULTS Two subjects have been treated at two corresponding dose levels (0.2mg/mL and 0.4 mg/mL). No dose-limiting toxicity or unexpected safety issues have been identified. To date, reported adverse events were mild (i.e., grade 1) and consistent with underlying disease and surgical procedures. No adverse events were attributed to OS2966 or CED catheter placement. Further, no clinically significant changes from baseline neurological exam have been noted for either patient through initial follow-up. Maximal tumor coverage and concomitant gross total resection were achieved for both patients. Tumor volume measured 1.63 cm3 and 16 cm3 for Patient 1 and 2 respectively with an intratumoral Vd/Vi ratio of 1.3. and 0.94. Pharmacodynamic analysis via tissue-level biomarkers is ongoing and will be presented. CONCLUSION Initial data demonstrates the safety and feasibility of direct intracranial delivery of OS2966.

A phase I study of convection-enhanced delivery of nanoliposomal irinotecan using real-time imaging in patients with recurrent high grade glioma.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. TPS2081-TPS2081
Author(s):  
Nicholas A. Butowski ◽  
Seunggu Han ◽  
Jennie Webster Taylor ◽  
Manish K. Aghi ◽  
Michael Prados ◽  
...  
Keyword(s):  
Phase I ◽  
Real Time ◽  
Phase I Study ◽  
High Grade Glioma ◽  
High Grade ◽  
Convection Enhanced Delivery ◽  
Real Time Imaging ◽  
Nanoliposomal Irinotecan

scholarly journals P27 * DEVELOPMENT OF AN IMPLANTABLE CATHETER AND BONE-ANCHORED PORT FOR INTERMITTENT CONVECTION-ENHANCED DELIVERY OF CARBOPLATIN FOR RECURRENT HIGH GRADE GLIOMA

2014 ◽  
Vol 16 (suppl 6) ◽  
pp. vi5-vi5
Author(s):  
N. U. Barua ◽  
M. Woolley ◽  
K. Hopkins ◽  
A. S. Bienemann ◽  
D. Cronin ◽  
...  
Keyword(s):  
High Grade Glioma ◽  
High Grade ◽  
Convection Enhanced Delivery

Regression of Recurrent Spinal Cord High-Grade Glioma After Convection-Enhanced Delivery of Nimustine Hydrochloride: Case Reports and Literature Review

2019 ◽  
Author(s):  
Toshiki Endo ◽  
Tomoo Inoue ◽  
Shinichiro Sugiyama ◽  
Ryuta Saito ◽  
Teiji Tominaga
Keyword(s):  
Spinal Cord ◽  
Case Reports ◽  
High Grade Glioma ◽  
Chemotherapeutic Agents ◽  
High Grade ◽  
Convection Enhanced Delivery ◽  
Thoracic Spinal Cord ◽  
Lower Extremity Weakness ◽  
Thoracic Spinal ◽  
Nimustine Hydrochloride

Abstract BACKGROUND Spinal cord high-grade glioma has poor prognosis. Especially, no treatment protocols have been established for recurrent cases. OBJECTIVE To apply a novel treatment method, convection-enhanced delivery (CED), for recurrent high-grade glioma. CED can deliver chemotherapeutic agents directly into the intramedullary lesion and possibly lead to remarkable regression of enlarging tumors that are, otherwise, difficult to control. METHODS Two patients developed high-grade glioma in the thoracic spinal cord. Partial resection and chemotherapy and radiotherapy induced remission of the disease. However, following the initial treatment, recurrence was noted in the spinal cord at 6 and 12 mo, respectively. No effective treatment was available for these recurrent lesions. Therefore, the authors decided to use CED to infuse nimustine hydrochloride (ACNU) directly into the spinal cord. During the procedure, the infusion cannula was inserted into the spinal cord lesion under intraoperative computed tomography scan. RESULTS After ACNU CED, successive magnetic resonance imaging confirmed remarkable shrinkages of the tumors in both cases. However, the patient's preinfusion symptoms, including bilateral lower extremity weakness, did not change after the treatment. Importantly, overall survivals of the 2 patients were as long as 67 and 33 mo. CONCLUSION The authors report the first 2 cases of recurrent spinal cord high-grade glioma. ACNU CED dramatically regressed enhanced mass lesions and provided local tumor controls in the spinal cord.

scholarly journals Convection enhanced delivery of tri-block copolymer nano-micelles: a method of direct intraparenchymal water-insoluble drug delivery for the treatment of high-grade glioma

2018 ◽  
Vol 20 (suppl_1) ◽  
pp. i19-i19
Author(s):  
Will Singleton ◽  
Andy Collins ◽  
Ali Bienemann ◽  
Clare Killick-Cole ◽  
Daniel Asby ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Block Copolymer ◽  
High Grade Glioma ◽  
High Grade ◽  
Convection Enhanced Delivery ◽  
Water Insoluble Drug

scholarly journals Convection-Enhanced Delivery of Nimustine Hydrochloride for Recurrent Spinal Cord High-grade Glioma

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Toshiki Endo ◽  
Ryuta Saito ◽  
Teiji Tominaga
Keyword(s):  
Spinal Cord ◽  
High Grade Glioma ◽  
Chemotherapeutic Agents ◽  
High Grade ◽  
Convection Enhanced Delivery ◽  
Thoracic Spinal Cord ◽  
Treatment Protocols ◽  
Lower Extremity Weakness ◽  
Thoracic Spinal ◽  
Nimustine Hydrochloride

Abstract INTRODUCTION Spinal cord high-grade glioma has poor prognosis. Especially, no treatment protocols have been established for recurrent cases.This paper describes a novel treatment method, convection enhanced delivery (CED), for recurrent high-grade glioma. CED can deliver chemotherapeutic agents directly into the intramedullary lesion and possibly lead remarkable regression of enlarging tumors that are otherwise difficult to control. METHODS Two patients developed high-grade glioma in the thoracic spinal cord. Partial resection and chemo- and radiotherapy-induced remission of the disease. However, following the initial treatment, recurrence was noted in the spinal cord 6 and 12 mo, respectively. No effective treatment was available for these recurrent lesions. Therefore, the authors decided to use CED to infuse nimustine hydrochloride (ACNU) directly into the spinal cord. During the procedure, the infusion cannula was inserted into the spinal cord lesion under intraoperative computed tomography scan. RESULTS After ACNU CED, successive magnetic resonance imaging confirmed remarkable shrinkages of the tumors in both cases. However, the patient's preinfusion symptoms including bilateral lower extremity weakness, did not change after the treatment. Importantly, overall survivals of the two patients were as long as 67 and 33 mo. CONCLUSION The authors report the first 2 cases of recurrent spinal cord high-grade glioma. ACNU CED dramatically regressed enhanced mass lesions and provided local tumor controls in the spinal cord.

An evaluation of the safety and feasibility of convection-enhanced delivery of carboplatin into the white matter as a potential treatment for high-grade glioma

2012 ◽  
Vol 108 (1) ◽  
pp. 77-88 ◽  
Author(s):  
Edward White ◽  
Alison Bienemann ◽  
John Pugh ◽  
Emma Castrique ◽  
Marcella Wyatt ◽  
...  
Keyword(s):  
White Matter ◽  
High Grade Glioma ◽  
High Grade ◽  
Potential Treatment ◽  
Convection Enhanced Delivery
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