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.

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.

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.

scholarly journals INNV-29. PHOTODYNAMIC THERAPY FOR MALIGNANT BRAIN TUMORS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi136-vi136
Author(s):  
Kazuhiro Tanaka ◽  
Takashi Sasayama ◽  
Tomoaki Nakai ◽  
Eiji Kohmura
Keyword(s):  
Photodynamic Therapy ◽  
Brain Tumors ◽  
Adverse Events ◽  
Tumor Invasion ◽  
Subtotal Resection ◽  
Diffusion Weighted Image ◽  
Mr Image ◽  
Malignant Brain Tumors ◽  
The Mean

Abstract INTRODUCTION Photodynamic therapy (PDT) uses the toxicity of singlet oxygen generated by a reaction between a photosensitizer in tumor cells and light with a specific wavelength. Recently, PDT for primary malignant brain tumors was approved in Japan. We retrospectively analyzed the patients treated with PDT in our hospital. METHODS From August 2017 to February 2019, total 16 patients were performed PDT in our hospital. After the tumor had been resected as extensively as possible, the region of probable tumor invasion in the resection cavity were irradiated superficially with a 664-nm diode laser for 180 sec (27 J/cm2) at a power density of 150 mW/cm. The characteristics of patients, the number of irradiation, adverse events, changes of the MR image, and clinical outcome were analyzed. RESULTS In histological examination, glioblastoma (GBM) were eleven cases, anaplastic oligodendroglioma were two cases, and other three cases were anaplastic astrocytoma, malignant meningioma, and malignant lymphoma. The mean tumor volume was 46.1 ml. Gross total resection, Subtotal resection, and partial resection were performed in 11 patients, 3 patents, and 2 patients, respectively. The mean number of laser irradiated sites was 15 (5~31 sites). Radiologically, the irradiated region indicated high intensity in diffusion-weighted image, which gradually disappeared for 2 weeks without neurological deterioration. In adverse events, venous congestion and brain swelling were observed in one patient. Three GBM patients were dead with tumor recurrence during a mean follow-up period of 24.4 months. CONCLUSION PDT was safe and useful for malignant brain tumors. However, PDT-induced specific changes in the tumor tissue should be monitored carefully.

scholarly journals Toxin-Based Targeted Therapy for Malignant Brain Tumors

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Vidyalakshmi Chandramohan ◽  
John H. Sampson ◽  
Ira Pastan ◽  
Darell D. Bigner
Keyword(s):  
Brain Tumors ◽  
Cytotoxic Agents ◽  
Treatment Modalities ◽  
Drug Candidates ◽  
Protein Conjugates ◽  
Malignant Brain Tumors ◽  
Disease Stabilization ◽  
Survival Prolongation ◽  
Specific Antigens ◽  
Cytotoxic Proteins

Despite advances in conventional treatment modalities for malignant brain tumors—surgery, radiotherapy, and chemotherapy—the prognosis for patients with high-grade astrocytic tumor remains dismal. The highly heterogeneous and diffuse nature of astrocytic tumors calls for the development of novel therapies. Advances in genomic and proteomic research indicate that treatment of brain tumor patients can be increasingly personalized according to the characteristics of the targeted tumor and its environment. Consequently, during the last two decades, a novel class of investigative drug candidates for the treatment of central nervous system neoplasia has emerged: recombinant fusion protein conjugates armed with cytotoxic agents targeting tumor-specific antigens. The clinical applicability of the tumor-antigen-directed cytotoxic proteins as a safe and viable therapy for brain tumors is being investigated. Thus far, results from ongoing clinical trials are encouraging, as disease stabilization and patient survival prolongation have been observed in at least 109 cases. This paper summarizes the major findings pertaining to treatment with the different antiglioma cytotoxins at the preclinical and clinical stages.

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.

scholarly journals Diagnosis of human cytomegvirus association with malignant gliomas and pro- and anti-inflammatories

2020 ◽  
Vol 33 (1) ◽  
pp. 14-16
Author(s):  
Fadyia Mahdi Muslim Alameedy ◽  
Abbas Raheem Jebur Al-mashhadi
Keyword(s):  
Brain Tumors ◽  
Real Time ◽  
Human Cytomegalovirus ◽  
Real Time Pcr ◽  
Malignant Gliomas ◽  
Control Group ◽  
Malignant Brain Tumors ◽  
Anti Inflammatory ◽  
True Infection

AbstractThe study was conducted on seventy individuals of both genders who have been exposed to human cytomegalovirus, a common illness in Iraq. Total cases of human cytomegvirus associated with malignant brain tumors were detected by a real time PCR technique. This resulted in only thirty-six cases of true infection. Of these 24 cases were female, while 12 cases of male infected. The titer to assay the presence of anti- and pro-inflammatories was assessed in sera of all patients by using ELISA kits to evaluate cytokines. This indicated that the pro-inflammatory IL12, after seven days increased (1.67±0.23 pg/ml), while IL4, an anti-inflammatory, decreased to reach (0.39±0.16 pg/ml) (at p<0.05) in the plasm of the experimental patients compared with the control group.

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