Phase II Trial of Thalidomide and Carmustine for Patients With Recurrent High-Grade Gliomas

2003 ◽  
Vol 21 (12) ◽  
pp. 2299-2304 ◽  
Author(s):  
Howard A. Fine ◽  
Patrick Y. Wen ◽  
Elizabeth A. Maher ◽  
Elene Viscosi ◽  
Tracy Batchelor ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Malignant Gliomas ◽  
Cytotoxic Agents ◽  
Clinical Activity ◽  
Antiangiogenic Agents ◽  
High Grade ◽  
Antiangiogenic Agent ◽  
Histologic Diagnosis ◽  
Anaplastic Gliomas ◽  
High Grade Gliomas

Purpose: The use of thalidomide as an antiangiogenic agent has met with only limited success in the treatment of malignant gliomas. On the basis of preclinical data demonstrating synergistic antitumor activity when antiangiogenic agents are combined with cytotoxic agents, we explored the clinical activity of the combination of thalidomide and carmustine (BCNU) in patients with recurrent high-grade gliomas. Patients and Methods: Patients with a histologic diagnosis of high-grade glioma and radiographic evidence of tumor progression after standard surgery, radiation, and chemotherapy were eligible for the study. Patients received BCNU 200 mg/m2 on day 1 of every 6-week cycle, and 800 mg/d of thalidomide that was escalated to a maximal dose of 1,200 mg/d as tolerated. Results: A total of 40 patients (38 with glioblastomas, two with anaplastic gliomas) were accrued to the study. The combination of thalidomide and BCNU was well tolerated; mild myelosuppression and mild to moderate sedation were the most common side effects. The median progression-free survival (100 days) and the objective radiographic response rate (24%) for patients with glioblastoma compared favorably with data from historical controls. Conclusion: This is one of the first clinical trials to evaluate the strategy of combining a putative antiangiogenic agent with a cytotoxic agent in patients with primary brain tumors. Our data demonstrate that thalidomide in combination with BCNU is well tolerated and has antitumor activity in patients with recurrent high-grade gliomas. Although the combination seems to be more active than either agent alone, such conclusions await confirmatory trials.

Phase II Trial of the Antiangiogenic Agent Thalidomide in Patients With Recurrent High-Grade Gliomas

2000 ◽  
Vol 18 (4) ◽  
pp. 708-708 ◽  
Author(s):  
Howard A. Fine ◽  
William D. Figg ◽  
Kurt Jaeckle ◽  
Patrick Y. Wen ◽  
Athanassios P. Kyritsis ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
External Beam Radiotherapy ◽  
Malignant Gliomas ◽  
Serum Levels ◽  
High Grade ◽  
Histologic Diagnosis ◽  
Glioma Growth ◽  
High Grade Gliomas

PURPOSE: Little progress has been made in the treatment of adult high-grade gliomas over the last two decades, thus necessitating a search for novel therapeutic strategies. Malignant gliomas are vascular or angiogenic tumors, which leads to the supposition that angiogenesis inhibition may represent a potentially promising strategy in the treatment of these tumors. We present the results of a phase II trial of thalidomide, a putative inhibitor of angiogenesis, in the treatment of adults with previously irradiated, recurrent high-grade gliomas. PATIENTS AND METHODS: Patients with a histologic diagnosis of anaplastic mixed glioma, anaplastic astrocytoma, or glioblastoma multiforme who had radiographic demonstration of tumor progression after standard external-beam radiotherapy with or without chemotherapy were eligible. Patients were initially treated with thalidomide 800 mg/d with increases in dose by 200 mg/d every 2 weeks until a final daily dose of 1,200 mg was achieved. Patients were evaluated every 8 weeks for response by both clinical and radiographic criteria. RESULTS: A total of 39 patients were accrued, with 36 patients being assessable for both toxicity and response. Thalidomide was well tolerated, with constipation and sedation being the major toxicities. One patient developed a grade 2 peripheral neuropathy after treatment with thalidomide for nearly a year. There were two objective radiographic partial responses (6%), two minor responses (6%), and 12 patients with stable disease (33%). Eight patients were alive more than 1 year after starting thalidomide, although almost all with tumor progression. Changes in serum levels of basic fibroblastic growth factor (bFGF) were correlated with time to tumor progression and overall survival. CONCLUSION: Thalidomide is a generally well-tolerated drug that may have antitumor activity in a minority of patients with recurrent high-grade gliomas. Future studies will better define the usefulness of thalidomide in newly diagnosed patients with malignant gliomas and in combination with radiotherapy and chemotherapy. Additionally, studies will be needed to confirm the potential utility of changes in serum bFGF as a marker of antiangiogenic activity and/or glioma growth.

scholarly journals Sonodynamic Therapy for the Treatment of Intracranial Gliomas

2021 ◽  
Vol 10 (5) ◽  
pp. 1101
Author(s):  
Antonio D’Ammando ◽  
Luca Raspagliesi ◽  
Matteo Gionso ◽  
Andrea Franzini ◽  
Edoardo Porto ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Therapeutic Option ◽  
Malignant Gliomas ◽  
Progression Free Survival ◽  
High Grade ◽  
Sonodynamic Therapy ◽  
Treatment Protocols ◽  
Ultrasound Waves ◽  
High Grade Gliomas ◽  
Preclinical And Clinical Studies

High-grade gliomas are the most common and aggressive malignant primary brain tumors. Current therapeutic schemes include a combination of surgical resection, radiotherapy and chemotherapy; even if major advances have been achieved in Progression Free Survival and Overall Survival for patients harboring high-grade gliomas, prognosis still remains poor; hence, new therapeutic options for malignant gliomas are currently researched. Sonodynamic Therapy (SDT) has proven to be a promising treatment combining the effects of low-intensity ultrasound waves with various sound-sensitive compounds, whose activation leads to increased immunogenicity of tumor cells, increased apoptotic rates and decreased angiogenetic potential. In addition, this therapeutic technique only exerts its cytotoxic effects on tumor cells, while both ultrasound waves and sensitizing compound are non-toxic per se. This review summarizes the present knowledge regarding mechanisms of action of SDT and currently available sonosensitizers and focuses on the preclinical and clinical studies that have investigated its efficacy on malignant gliomas. To date, preclinical studies implying various sonosensitizers and different treatment protocols all seem to confirm the anti-tumoral properties of SDT, while first clinical trials will soon start recruiting patients. Accordingly, it is crucial to conduct further investigations regarding the clinical applications of SDT as a therapeutic option in the management of intracranial gliomas.

Impact of Prognostic Nutritional Index on Survival in Recurrent High-Grade Glial Tumors Treated with Systemic Treatment

2020 ◽  
Author(s):  
Ozkan Alan ◽  
Tugba Akin Telli ◽  
Tugba Basoglu ◽  
Rukiye Arikan ◽  
Nazim Can Demircan ◽  
...  
Keyword(s):  
Lymphocyte Count ◽  
Systemic Treatment ◽  
Prognostic Nutritional Index ◽  
High Grade Glioma ◽  
High Grade ◽  
Prognostic Role ◽  
Nutritional Index ◽  
Anaplastic Gliomas ◽  
High Grade Gliomas ◽  
Rare Malignancy

Abstract Background: Primary brain tumors are relatively rare malignancy, with high-grade gliomas (glioblastoma multiforme and anaplastic gliomas) are the most common types . We aimed to evaluate the prognostic value of Prognostic Nutritional Index (PNI), which is calculated by lymphocyte count and albumin, in recurrent high-grade glioma patients treated with systemic treatment.Methods: Data of 92 patients with recurrent high-grade glioma who received systemic treatment and followed in our clinic between 2012-2018 was retrospectively collected and analyzed. PNI was calculated as: [(10 × serum albumin (g/dL)) + (0.005 × total lymphocyte count)]. Patients were categorized according to the median PNI value. We investigated the prognostic role of PNI groups, and survival outcomes.Results: Median value of PNI was 46.02, and median follow-up duration was 9 months (1-68 months). Median overall survival (OS) was 8.1 months (95%CI: 6.04-10.3). Median OS was significantly longer in patients with PNI> 46.02 compared to patients with PNI ≤ 46.02 (13.9 months (95%CI: 9.8-18.1), and 6.07 months (95%CI: 4.3-7.7), p=0.01, respectively). In multivariate analysis, PNI was found to be an independent prognostic factor for OS [HR:0.54(95%CI:0.3-0.97), p=0.03)].Conclusion: In our study, the PNI was found to be an independent prognostic biomarker in patients with recurrent high-grade gliomas, but further prospective trials are necessary to validate its prognostic role.

Current strategies for the treatment of malignant gliomas – experience of the Department of Neurosurgery, Brodno Masovian Hospital in Warsaw

2020 ◽  
Vol 92 (4) ◽  
pp. 1-5
Author(s):  
Grzegorz Turek ◽  
Tomasz Pasterski ◽  
Krzysztof Bankiewicz ◽  
Sebastian Dzierzęcki ◽  
Mirosław Ząbek
Keyword(s):  
Brain Tumors ◽  
San Francisco ◽  
Malignant Gliomas ◽  
High Grade ◽  
Current Standard ◽  
Convection Enhanced Delivery ◽  
Surgical Methods ◽  
High Grade Gliomas ◽  
Standard Medical Treatment ◽  
Intraoperative Electrical Stimulation

Introduction: Malignant gliomas (HGG) are the most common primary malignant brain tumors arising from glial cells. Between HGG, glioblastoma is the most common and the most malignant histological subtype with only a 27% 2-year survival rate. Current standard medical treatment of malignant gliomas is still not satisfactory, and may need some development and modification. We presented and discussed the achievements of the Department of Neurosurgery at Brodno Masovian Hospital in the treatment of malignant gliomas. Material and methods: We step by step presented and discussed the policy in the treatment of malignant gliomas. We showed all steps starting from preparation of surgery (eg. neuroimaging) and finishing on the presentation the development of perioperative management – from intraoperative electrical stimulation mapping and monitoring which is nowadays already standard method to convection-enhanced delivery (CED) and gamma knife (GK) which are new and promising methods in the treatment of glioblastoma. Results: All surgical methods described in this manuscript were introduced to achieve maximal and safe resection of malignant glioma. CED and GK are the last resort methods for patients with recurrent HGG. Discussion: Department of Neurosurgery at Brodno Masovian Hospital deal with all types of brain tumors, including all types of high grade gliomas. As the first Department in Europe with close cooperation with the Department of Neurosurgery in San Francisco, we have started local infusions of drugs directly to the tumor in the real time of magnetic field, and we think that technology may change all approaches to the treatment of high grade gliomas.

scholarly journals Mismatch-Repair Protein Expression in High-Grade Gliomas: A Large Retrospective Multicenter Study

2020 ◽  
Vol 21 (18) ◽  
pp. 6716 ◽  
Author(s):  
Mario Caccese ◽  
Tamara Ius ◽  
Matteo Simonelli ◽  
Matteo Fassan ◽  
Daniela Cesselli ◽  
...  
Keyword(s):  
Protein Expression ◽  
Mismatch Repair ◽  
Complete Loss ◽  
Molecular Characteristics ◽  
High Grade ◽  
Dna Mismatch ◽  
Anaplastic Gliomas ◽  
High Grade Gliomas ◽  
Mmr Proteins

Background: DNA mismatch repair (MMR) is a system for repairing errors in DNA replication. Cancer cells with MMR deficiency can have immunohistochemical loss of MMR protein expression leading to a hypermutable phenotype that may correlate with anti-PD1 efficacy. Scant data exist about immunohistochemical loss of MMR protein expression in high-grade gliomas (HGG). Materials and Methods: We performed a large multicenter retrospective study to investigate the frequency and the prognostic role of immunohistochemical loss of MMR protein expression in HGG patients; we nevertheless evaluated the association between this status and clinical or molecular characteristics. Immunohistochemical loss of MMR protein expression was recorded as partial or complete loss of at least 1 MMR protein. Results: We analyzed the expression of MMR proteins in tumor tissue of 355 consecutive patients. Partial and complete immunohistochemical loss of MMR proteins was found in 43/355 samples (12.1%) and among these, 15 cases (4.2%) showed a complete loss of at the least one MMR protein. Alteration of MSH2 expression was found in 55.8%, MSH6 in 46.5%, PMS2 in 34.9%, and MLH1 in 30.2%. Alteration of MMR protein expression was statistically more frequent in anaplastic gliomas, in recurrent disease, in patients treated with temozolomide, and in IDH-mut gliomas. Immunohistochemical loss of MMR proteins was not associated with survival, adjusting for clinically relevant confounders. Conclusions: MMR protein expression status did not affect survival in HGG patients. We identified clinical and molecular characteristics correlating with immunohistochemical loss of MMR proteins expression. A large study should be performed to analyze its predictive role of immune checkpoint inhibitor efficacy in these subgroups of patients.

Antiangiogenic therapy using bevacizumab in recurrent high-grade glioma: impact on local control and patient survival

2009 ◽  
Vol 110 (1) ◽  
pp. 173-180 ◽  
Author(s):  
Ashwatha Narayana ◽  
Patrick Kelly ◽  
John Golfinos ◽  
Erik Parker ◽  
Glyn Johnson ◽  
...  
Keyword(s):  
Patient Survival ◽  
Chemotherapeutic Agent ◽  
Antiangiogenic Therapy ◽  
Progression Free Survival ◽  
High Grade Glioma ◽  
Median Number ◽  
Antiangiogenic Agents ◽  
High Grade ◽  
Diffuse Disease ◽  
High Grade Gliomas

Object Antiangiogenic agents have recently shown impressive radiological responses in high-grade glioma. However, it is not clear if the responses are related to vascular changes or due to antitumoral effects. The authors report the mature results of a clinical study of bevacizumab-based treatment of recurrent high-grade gliomas. Methods Sixty-one patients with recurrent high-grade gliomas received treatment with bevacizumab at 10 mg/ kg every 2 weeks for 4 doses in an 8-week cycle along with either irinotecan or carboplatin. The choice of concomitant chemotherapeutic agent was based on the number of recurrences and prior chemotherapy. Results At a median follow-up of 7.5 months (range 1–19 months), 50 (82%) of 61 patients relapsed and 42 patients (70%) died of the disease. The median number of administered bevacizumab cycles was 2 (range 1–7 cycles). The median progression-free survival (PFS) and overall survival (OS) were 5 (95% confidence interval [CI] 2.3–7.7) and 9 (95% CI 7.6–10.4) months, respectively, as calculated from the initiation of the bevacizumab-based therapy. Radiologically demonstrated responses following therapy were noted in 73.6% of cases. Neither the choice of chemotherapeutic agent nor the performance of a resection prior to therapy had an impact on patient survival. Although the predominant pattern of relapse was local, 15 patients (30%) had diffuse disease. Conclusions Antiangiogenic therapy using bevacizumab appears to improve survival in patients with recurrent high-grade glioma. A possible change in the invasiveness of the tumor following therapy is worrisome and must be closely monitored.

scholarly journals ONCOLYTIC VIRUSES IN HIGH-GRADE GLIOMAS TREATMENT

2015 ◽  
Vol 6 (2) ◽  
pp. 46-59 ◽  
Author(s):  
V P Baklaushev ◽  
S A Goryainov ◽  
А А Potapov ◽  
G V Pavlova ◽  
V P Chehonin
Keyword(s):  
Clinical Trials ◽  
Clinical Guidelines ◽  
Laboratory Tests ◽  
State Of The Art ◽  
Malignant Gliomas ◽  
Point Of View ◽  
Oncolytic Viruses ◽  
High Grade ◽  
Preclinical Trials ◽  
High Grade Gliomas

The review examines the state of the art of diagnosis and therapy of high-grade gliomas both by currently existing clinical guidelines, and from the point of view of the most promising approaches of currently undergoing laboratory tests and the first clinical trials. One of the most promising approach for the treatment of malignant gliomas is the nonpathogenic oncolytic viruses (OV) application. The data of preclinical trials of OV and the first preliminary results of clinical trials are discussed.

scholarly journals Fusion Genes Altered in Adult Malignant Gliomas

2021 ◽  
Vol 12 ◽  
Author(s):  
Gan You ◽  
Xing Fan ◽  
Huimin Hu ◽  
Tao Jiang ◽  
Clark C. Chen
Keyword(s):  
Genetic Background ◽  
Molecular Genetic ◽  
Malignant Gliomas ◽  
Therapeutic Targets ◽  
High Grade ◽  
Gene Fusions ◽  
Fusion Genes ◽  
High Grade Gliomas ◽  
The Many

Malignant gliomas are highly heterogeneous brain tumors in molecular genetic background. Despite the many recent advances in the understanding of this disease, patients with adult high-grade gliomas retain a notoriously poor prognosis. Fusions involving oncogenes have been reported in gliomas and may serve as novel therapeutic targets to date. Understanding the gene fusions and how they regulate oncogenesis and malignant progression will contribute to explore new approaches for personalized treatment. By now, studies on gene fusions in gliomas remain limited. However, some current clinical trials targeting fusion genes have presented exciting preliminary findings. The aim of this review is to summarize all the reported fusion genes in high-grade gliomas so far, discuss the characterization of some of the most popular gene fusions occurring in malignant gliomas, as well as their function in tumorigenesis, and the underlying clinical implication as therapeutic targets.

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