scholarly journals Implantable Slow-Release Chemotherapeutic Polymers for the Treatment of Malignant Brain Tumors

1998 ◽  
Vol 5 (2) ◽  
pp. 130-137 ◽  
Author(s):  
Prakash Sampath ◽  
Henry Brem
Keyword(s):  
Brain Tumors ◽  
Slow Release ◽  
Malignant Gliomas ◽  
Polymer System ◽  
Chemotherapeutic Agents ◽  
Local Concentration ◽  
Malignant Brain Tumors ◽  
Polymeric Delivery ◽  
Double Blinded ◽  
Controlled Release Polymer

Background: Despite significant advances in neurosurgery, radiation therapy, and chemotherapy, the prognosis for patients with malignant brain tumors remains dismal. In an effort to improve control of local disease, we have developed a biodegradable, controlled-release polymer that is implanted directly at the tumor site. Methods: The preclinical and clinical development of the polymeric delivery of chemotherapeutic agents for treatment of patients with malignant gliomas is reviewed. Results: Carmustine (BCNU)-impregnated biodegradable polymer is the first new therapy approved by the FDA for patients with gliomas in 23 years. This delivery system provides high local concentration of drug with minimal systemic toxicity and obviates the need for drug to cross the blood-brain barrier. Randomized, multi-institutional, double-blinded, placebo-controlled studies have shown improved survival in patients treated for gliomas both at initial presentation and at recurrence. Several clinical principles have emerged from the use of this polymer system, and further applications are currently being investigated. Conclusions: Local delivery of therapeutic agents via biodegradable polymers may play an increasing role in patients with brain tumors.

Cytostatic Agents in the Management of Malignant Gliomas

1998 ◽  
Vol 5 (2) ◽  
pp. 150-162 ◽  
Author(s):  
Tom Mikkelsen
Keyword(s):  
Signal Transduction ◽  
Brain Tumors ◽  
Tumor Invasion ◽  
Proteinase Inhibitors ◽  
Malignant Gliomas ◽  
Cytotoxic Agents ◽  
Management Approach ◽  
Cytostatic Agents ◽  
Management Options ◽  
Malignant Brain Tumors

Background: Cytotoxic therapy for malignant gliomas is limited by poor delivery and drug resistance, and local therapy is ineffective in managing migratory cells. However, recent developments in malignant glioma therapy involve trials of cytostatic rather than conventional cytotoxic agents. Methods: The biology of the brain extracellular matrix, tumor invasion, and angiogenesis are reviewed, and the cytostatic agents that inhibit matrix metalloproteinases, angiogenesis, cell proliferation, and signal transduction are discussed, as well as studies of the angiogenic and migratory capacity of malignant brain tumors. Results: Two specific and interrelated areas, anti-invasion (migration) and anti-angiogenesis, are potential areas to develop new treatment strategies. Tumor invasion and angiogenesis are important components of the spread and biologic effects of malignant gliomas. Several proteinase inhibitors are in clinical trial, as well as anti-angiogenic agents and signal transduction cascade inhibitors. Conclusions: Biologic control of brain tumor cell populations may offer a new management approach to add to currently available management options for malignant brain tumors.

Hyperthermia for Brain Tumors

Neurosurgery ◽  
1981 ◽  
Vol 9 (3) ◽  
pp. 327-335 ◽  
Author(s):  
Michael Salcman ◽  
George M. Samaras
Keyword(s):  
Brain Tumors ◽  
Thermal Sensitivity ◽  
Antineoplastic Agent ◽  
Therapeutic Index ◽  
Chemotherapeutic Agents ◽  
Cellular Level ◽  
Growth Fraction ◽  
Combined Modality Treatment ◽  
Clinical Safety ◽  
Malignant Brain Tumors

Abstract Hyperthermia has great potential as an antineoplastic agent because: (a) it is effective against relatively radioresistant hypoxic cells and cells in S phase: (b) unlike most chemotherapeutic agents. it is effective against poorly vascularized and metabolically quiescent tissues; (c) as a physical agent, its biological effect is related to the duration and intensity of its application; (d) it seems to have no cumulative toxicity; and (e) it potentiates the effects of both chemotherapy and ionizing radiation at the cellular level. The use of hyperthermia for malignant brain tumors is constrained by a relatively narrow therapeutic index and the considerable thermal sensitivity of normal neural tissue. Glioblastoma multiforme, by virtue of its low growth fraction and heterogeneous cell populations, seems to be an ideal candidate for hyperthermia administered as part of a combined modality treatment program. Focal hyperthermia can be produced by a number of energy sources, including those utilizing ultrasound, microwave, and radiofrequency generators. The clinical safety and feasibility of a miniature microwave radiator/sensor system for direct implantation have been demonstrated. In comparison to normal feline brain, malignant brain tumors in humans are unable to dissipate heat efficiently.

Glioblastoma: Background, Standard Treatment Paradigms, and Supportive Care Considerations

2014 ◽  
Vol 42 (2) ◽  
pp. 171-182 ◽  
Author(s):  
Susan V. Ellor ◽  
Teri Ann Pagano-Young ◽  
Nicholas G. Avgeropoulos
Keyword(s):  
Central Nervous System ◽  
Brain Tumors ◽  
Standard Treatment ◽  
Malignant Gliomas ◽  
Survival Rates ◽  
Terminally Ill ◽  
Ethical Considerations ◽  
The Third ◽  
Malignant Brain Tumors ◽  
Median Survival Rate

While primary malignant brain tumors account for only two percent of all adult cancers, these neoplasms cause a disproportionate amount of cancer-related disabilities and death. The five-year survival rates for brain tumors are the third lowest among all types of cancer. Malignant gliomas (glioblastoma and anaplastic astrocytoma) comprise the most common types of primary central nervous system (CNS) tumors and have a combined incidence of five to eight cases per 100,000 people. The median survival rate of conservatively treated patients with malignant gliomas is 14 weeks; with surgical resection alone, 20 weeks; with surgery and radiation, 36 weeks; and with the addition of newer biochemotherapies such as temozolomide and bevacizumab, upward of 14-18 months.The profound cost of caring for terminally ill patients with primary malignant brain tumors raises ethical considerations for the American public; the stewardship of health care dollars for the population at large maintains a juxtaposed tension against a dynamic, necessary balance of hope, care, rehabilitation and research efforts for affected patients and their advocates.

Bevacizumab, a monoclonal antibody to the vascular endothelial growth factor (VEGF), and irinotecan for treatment of recurrent primary malignant brain tumors in adults

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 12503-12503 ◽  
Author(s):  
U. Lassen ◽  
K. Grunnet ◽  
M. Kosteljanetz ◽  
B. Hasselbalch ◽  
H. Laursen ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Tumor Regression ◽  
Malignant Gliomas ◽  
Complete Response ◽  
Consecutive Series ◽  
Topoisomerase 1 ◽  
Malignant Brain Tumors ◽  
Macdonald Criteria ◽  
Number Of Patients ◽  
Tumor Reduction

12503 Background: The prognosis of recurrent malignant brain tumors is poor, and no efficacious therapy exists in patients previously treated with radiotherapy and standard chemotherapy. Bevacizumab (B) binds to VEGF and inhibits tumor angiogenesis, and treatment with this drug might induce tumor regression and prolongation of life. Irinotecan (I) is a topoisomerase 1 inhibitor with modest effect on recurrent primary brain tumors. The combination of B and I in recurrent malignant gliomas was presented at ASCO 2006 and showed very encouraging responses. Methods: We report confirmatory results of the combination of B and I in a consecutive series of patients with primary malignant brain tumors recurring after standard primary and secondary treatment (surgery, radiotherapy and standard or secondline chemotherapy).With standard inclusion criteria, including PS 0–2, patients received B as 10mg/kg, and I 125 mg/m2 in patients not treated with enzyme inducing antiepileptic drugs (EIAED) or 340 mg/m2 in patients treated with EIAED every other week until progression or non-manageable toxicity. Response evaluation was performed by MacDonald criteria and MRI scans. Results: The results of 31 patients is presented, 15 with grade IV tumors (Glioblastoma multiforme), 7 with grade III anaplastic astrocytomas, 5 with anaplastic oligodendrogliomas, 1 with anaplastic ependymoma, 1 with hemangiopericytoma, 1 with prolactinoma, and 1 with medulloblastoma. Four patients had complete response, 3 grade IV tumors and 1 anaplastic oligodendroglioma. One patient had partial response (> 50% tumor reduction), 12 had stable disease (3 had tumor reduction between 31 - 45 %). 14 progressed. No grade 4 toxicity was observed and most patients experienced grade 1–2 toxicity. Two tromboembolic events and 1 intestinal perforation were observed. Conclusion: The combination of B and I is safe, induces tumor regression in a substantial number of patients, and can be used as treatment to patients recurring after standard treatment. No significant financial relationships to disclose.

Novel Advances in Drug Delivery to Brain Cancer

2005 ◽  
Vol 4 (4) ◽  
pp. 417-428 ◽  
Author(s):  
Maciej S. Lesniak
Keyword(s):  
Drug Delivery ◽  
Brain Tumors ◽  
Tumor Therapy ◽  
Chemotherapeutic Agents ◽  
Controlled Delivery ◽  
Local Drug Delivery ◽  
Delivery Methods ◽  
Malignant Brain Tumors ◽  
Direct Exposure ◽  
The Brain

The therapy of brain tumors has been limited by a lack of effective methods of drug delivery to the brain. Systemic administration is often associated with toxic side effects and ultimately fails to achieve therapeutic concentrations within a tumor. An attractive strategy that has gained importance in brain tumor therapy has relied on local and controlled delivery of chemotherapeutic agents by biodegradable polymers. This technique allows direct exposure of tumor cells to a therapeutic agent for a prolonged period of time and has been shown to prolong the survival of patients with malignant brain tumors. The use of polymers for local drug delivery greatly expands the spectrum of drugs available for the treatment of malignant brain tumors. This review discusses the rationale for local drug delivery, describes the development of currently available polymer-based therapeutic agents, and highlights examples of promising non-polymer based drug delivery methods for use in the treatment of malignant brain tumors.

scholarly journals DDEL-03. LONG-TERM INTRAVENTRICULAR THERAPY ALTERNATING ETOPOSIDE AND LIPOSOMAL CYTARABINE: EXPERIENCE IN 75 CHILDREN AND ADOLESCENTS WITH MALIGNANT BRAIN TUMORS

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii284-iii284
Author(s):  
Natalia Stepien ◽  
Andreas Peyrl ◽  
Amedeo Azizi ◽  
Johannes Gojo ◽  
Lisa Mayr ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Tumor Cells ◽  
Slow Release ◽  
Intrathecal Therapy ◽  
Liposomal Cytarabine ◽  
Release Formulation ◽  
Malignant Brain Tumors ◽  
Slow Release Formulation ◽  
Anti Cancer

Abstract BACKGROUND Malignant brain tumors of childhood carry a high risk for leptomeningeal dissemination and tumor cells floating in the CSF are often not amenable to systemic and/or antiangiogenic chemotherapy. We report on our experience with an intraventricular therapy consisting of alternating cycles of liposomal cytarabine and etoposide. PATIENTS AND METHODS Between 2004 and 2017, 75 patients aged 0.6 to 22 years (median 11) with various malignant brain tumors received intraventricular etoposide 0.25mg (<1year) - 0.5mg on five consecutive days alternating with liposomal cytarabine at a dose of 25mg (<3 years) - 50mg via an Ommaya reservoir. RESULTS 5533 doses of etoposide (5–277/patient, median 141) corresponding to 1–56 five-day-cycles/patient alternating with 534 doses of liposomal cytarabine (1–21/patient, median 11) were administered. Treatment was given over a period of 1 – 146 months (median 73.5). Toxicities did occur but were infrequent and mostly mild. Since all patients received some sort of concurrent anti-cancer therapy, the efficacy of intrathecal therapy cannot be assessed independently. However, 29/75 patients are still alive, and none of the patients had tumor cells in the CSF at their last evaluation. CONCLUSION In conclusion, alternating intraventricular liposomal cytarabine and etoposide produced responses and proved to be an important adjunct for patients receiving drugs with a low penetrance into the CSF. Since production of liposomal cytarabine was discontinued in 2017 it remains to be determined whether substitution of the slow release formulation by aqueous cytarabine on days 1, 4, 8, and 11 may produce similar results.

scholarly journals Genetic Alterations in Gliomas Remodel the Tumor Immune Microenvironment and Impact Immune-Mediated Therapies

2021 ◽  
Vol 11 ◽  
Author(s):  
Maria B. Garcia-Fabiani ◽  
Santiago Haase ◽  
Andrea Comba ◽  
Stephen Carney ◽  
Brandon McClellan ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Current Knowledge ◽  
Malignant Gliomas ◽  
Standard Of Care ◽  
Genetic Alterations ◽  
Immune Microenvironment ◽  
Malignant Brain Tumors ◽  
Immune Mediated ◽  
Tumor Immune Microenvironment ◽  
The Impact

High grade gliomas are malignant brain tumors that arise in the central nervous system, in patients of all ages. Currently, the standard of care, entailing surgery and chemo radiation, exhibits a survival rate of 14-17 months. Thus, there is an urgent need to develop new therapeutic strategies for these malignant brain tumors. Currently, immunotherapies represent an appealing approach to treat malignant gliomas, as the pre-clinical data has been encouraging. However, the translation of the discoveries from the bench to the bedside has not been as successful as with other types of cancer, and no long-lasting clinical benefits have been observed for glioma patients treated with immune-mediated therapies so far. This review aims to discuss our current knowledge about gliomas, their molecular particularities and the impact on the tumor immune microenvironment. Also, we discuss several murine models used to study these therapies pre-clinically and how the model selection can impact the outcomes of the approaches to be tested. Finally, we present different immunotherapy strategies being employed in clinical trials for glioma and the newest developments intended to harness the immune system against these incurable brain tumors.

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