scholarly journals Current FDA-Approved Therapies for High-Grade Malignant Gliomas

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 324
Author(s):  
Jacob P. Fisher ◽  
David C. Adamson
Keyword(s):  
Controlled Trial ◽  
Malignant Gliomas ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
High Grade ◽  
Tumor Treatment ◽  
Free Survival ◽  
Randomized Controlled ◽  
Significant Survival ◽  
One Year

The standard of care (SOC) for high-grade gliomas (HGG) is maximally safe surgical resection, followed by concurrent radiation therapy (RT) and temozolomide (TMZ) for 6 weeks, then adjuvant TMZ for 6 months. Before this SOC was established, glioblastoma (GBM) patients typically lived for less than one year after diagnosis, and no adjuvant chemotherapy had demonstrated significant survival benefits compared with radiation alone. In 2005, the Stupp et al. randomized controlled trial (RCT) on newly diagnosed GBM patients concluded that RT plus TMZ compared to RT alone significantly improved overall survival (OS) (14.6 vs. 12.1 months) and progression-free survival (PFS) at 6 months (PFS6) (53.9% vs. 36.4%). Outside of TMZ, there are four drugs and one device FDA-approved for the treatment of HGGs: lomustine, intravenous carmustine, carmustine wafer implants, bevacizumab (BVZ), and tumor treatment fields (TTFields). These treatments are now mainly used to treat recurrent HGGs and symptoms. TTFields is the only treatment that has been shown to improve OS (20.5 vs. 15.6 months) and PFS6 (56% vs. 37%) in comparison to the current SOC. TTFields is the newest addition to this list of FDA-approved treatments, but has not been universally accepted yet as part of SOC.

Clinical Equipoise for Trials of Novel Biologic Therapies, Therapeutic Success Rates, and Predictors of Success: A Meta-Analysis

2017 ◽  
pp. 1-12
Author(s):  
Doah Cho ◽  
Felicia T. Roncolato ◽  
Johnathan Man ◽  
John Simes ◽  
Sarah J. Lord ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Predictors Of Success ◽  
Biologic Therapies ◽  
Therapeutic Success ◽  
Free Survival ◽  
Randomized Controlled ◽  
Phase Iii Trials

Purpose The demand for more rapid access to novel biologic therapies than randomized controlled trials can deliver is a topic of ongoing study and debate. We aimed to inform this debate by estimating therapeutic success from phase III trials comparing novel biologic therapies with standard of care and identifying predictors of success. Methods This was a meta-analysis of phase III trials evaluating novel biologic therapies in advanced breast, colorectal, lung, and prostate cancers. Therapeutic success was defined as statistically significant results for the primary end point favoring novel biologic therapies. Results Of 119 included phase III trials (76,726 patients), therapeutic success was 41%, with a statistically significant relative reduction in disease progression and death for novel biologic therapies over standard of care of 20% and 8%. Therapeutic success did not improve over time (pre-2010, 33%; 2010 to 2014, 44%; P = .2). Predictors of success were a biomarker-selected population (odds ratio, 4.74; 95% CI, 2.05 to 10.95) and progression-free survival end point compared with overall survival (odds ratio, 5.22; 95% CI, 2.41 to 11.39). Phase III trials with a biomarker-selected population showed a larger 28% progression-free survival benefit than phase III trials overall (hazard ratio, 0.72; 95% CI, 0.70 to 0.75) but similar 8% overall survival benefit (hazard ratio, 0.92; 95% CI, 0.90 to 0.94). Therapeutic success of phase III trials with and without a preceding phase II trial were 43% and 30%, respectively Conclusion Therapeutic success of novel biologic therapies in phase III trials, including therapies with a matching predictive biomarker, was modest and has not significantly improved over time. Equipoise remains and supports the ongoing ethical and scientific requirement for phase III randomized controlled trials to estimate treatment efficacy and assess the value of potential biomarkers.

scholarly journals Randomized Controlled Trial of Interval-Compressed Chemotherapy for the Treatment of Localized Ewing Sarcoma: A Report From the Children's Oncology Group

2012 ◽  
Vol 30 (33) ◽  
pp. 4148-4154 ◽  
Author(s):  
Richard B. Womer ◽  
Daniel C. West ◽  
Mark D. Krailo ◽  
Paul S. Dickman ◽  
Bruce R. Pawel ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Ewing Sarcoma ◽  
Primary Tumor ◽  
Controlled Trial ◽  
Tumor Treatment ◽  
Free Survival ◽  
Randomized Controlled ◽  
Prospective Randomized Controlled Trial ◽  
Treatment Surgery ◽  
Median Interval

Purpose Chemotherapy with alternating vincristine-doxorubicin-cyclophosphamide and ifosfamide-etoposide cycles and primary tumor treatment with surgery and/or radiation therapy constitute the usual approach to localized Ewing sarcoma in North America. We tested whether chemotherapy intensification through interval compression could improve outcome. Patients and Methods This was a prospective, randomized controlled trial for patients younger than 50 years old with newly diagnosed localized extradural Ewing sarcoma. Patients assigned to standard and intensified treatment were to begin chemotherapy cycles every 21 and 14 days, respectively, provided an absolute neutrophil count greater than 750 × 106/L and a platelet count greater than 75 × 109/L. Patients received vincristine (2 mg/m2), doxorubicin (75 mg/m2), and cyclophosphamide (1.2 g/m2) alternating with ifosfamide (9 g/m2) and etoposide (500 mg/m2) for 14 cycles, with filgrastim (5 mg/kg per day; maximum, 300 mg) between cycles. Primary tumor treatment (surgery, radiation, or both) was to begin at week 13 (after four cycles in the standard arm and six cycles in the intensified arm). The primary end point was event-free survival (EFS). The study is registered at ClinicalTrials.gov (identifier: NCT00006734). Results Five hundred eighty-seven patients were enrolled and randomly assigned, and 568 patients were eligible, with 284 patients in each regimen. For all cycles, the median cycle interval for standard treatment was 21 days (mean, 22.45 days); for intensified treatment, the median interval was 15 days (mean, 17.29 days). EFS at a median of 5 years was 65% in the standard arm and 73% in the intensified arm (P = .048). The toxicity of the regimens was similar. Conclusion For localized Ewing sarcoma, chemotherapy administered every 2 weeks is more effective than chemotherapy administered every 3 weeks, with no increase in toxicity.

High-grade glioma of central nervous system: Single center treatment experience.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14040-e14040
Author(s):  
Nur Olgun ◽  
Deniz Kızmazoğlu ◽  
Batuhan Özdoğar ◽  
Emre Çeçen ◽  
Ceren Kızmazoğlu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Rates ◽  
Progression Free Survival ◽  
High Grade Glioma ◽  
High Grade ◽  
Event Free Survival ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
One Year ◽  
Overall Survival Rates

e14040 Background: To evaluate characteristics and treatment responses of patients with high grade gliomas (HGG) in our center Methods: Medical files of patients with malignant CNS tumors between 1987-2020 were analyzed retrospectively. There were 44 patients with HGG. Results: Diagnosis of patients as follows: 21 pons glioma, 2 anaplastic astrocytoma, 11 anaplastic ependimoma, 7 glioblastoma multiforme, 1 glioblastoma, 2 gliomatosis cerebri. The median age at diagnosis was 6,5 yrs (7 – 17 yrs), M/F:25/19. Age distrubution: <5 yrs 12 patients, 5-10 yrs 18 patients, 10-18 yrs 14 patients. The most frequent complaints for pons gliomas: cranial nerve paralysis (52%), visial impairment (48%), headache (38%), power loss (43%) and speech disorder (30%). Surgery was performed to extrinsic component of mass in 3 patients of pons gliomas. For other HGG: 7 subtotal resection and 16 gross total resection had performed. Seven patients died before RT. And other 37 patients received radiotherapy. RT total doses varied between 50-60 Gy. Seven patients were not received chemotherapy, 3 of them died before chemo, and others received only RT. Chemotherapy protocoles were changed over the years: For pons gliomas, MOPP (Mechlorethamine, vincristine, prednisone, procarbazine) in 3 patients, NOPP (nitrosourea, vincristine, prednisone, procarbazine) in 2 patients, only ICE (Ifosfamide, carboplatin, cisplatin) in five patients, oral cyclophosphamide in one patient, temozolamide in one patient and temo + bevacizumab in one patient. Last 3 patients received nimotuzumab-vinorelbine after ICE and temo. For other HGGs, platin based regimens used fort he first line treatment. Temozolamide-bevacizumab, irinotecan-temsirolimus combinations were the other options as second and also third line treatments. Median progression free survival time was 6 mos (2 weeks -25 mos) for pons gliomas, for other gliomas median progression free survival time was 14 mos (0 -74 mos). For pons gliomas: Event free survival rate for 6 mos was 75%, for one year was 17%, One year, 18 mos, and two years overall survival rates were 84%, 52% and 10% respectively. For other HGGs: Event free survival rate for one year and two years were 57% and 17% respectively. One year and two years overall survival rates were 73% and 36% respectively. Conclusions: High grade glioma is a group of tumor in which still the helplessness experienced in treatment. Despite radiotherapy and chemotherapy, prognosis is very poor. The progression free and overall survival rates of patients were similar to literature. With new developments in molecular pathology, as the use of molecular target therapies, the progression free survival rates newly will improve.

The Role of Imatinib Following Complete Resection of Primary Gastrointestinal Stromal Tumors

2009 ◽  
Vol 05 (01) ◽  
pp. 58
Author(s):  
Burton L Eisenberg ◽  
Keyword(s):  
Adjuvant Therapy ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
High Rate ◽  
Free Survival ◽  
Primary Gist ◽  
Life Threatening ◽  
One Year ◽  
Malignant Gists

Gastrointestinal stromal tumor (GIST) is a life-threatening disease, for which surgery is the standard of care. However, surgical resection of the primary tumor is associated with a high rate of recurrence and a low five-year overall survival (OS) rate. The introduction of the KIT protein kinase-targeted therapy imatinib mesylate has enhanced treatment options. It has demonstrated improvements in progression-free survival and OS in patients with unresectable and/or metastatic malignant GISTs. Based on this efficacy, imatinib has been evaluated as an adjuvant option in KIT-positive primary GIST patients who have undergone complete gross resection. Early data indicate that one-year adjuvant therapy with imatinib 400mg/day can prolong recurrence-free survival (RFS) in these patients. Preliminary data also indicate potential benefits of a higher imatinib dose (800mg/day) and a longer duration of adjuvant imatinib therapy. Currently, imatinib, at a recommended dose of 400mg/day, is approved by the US Food and Drug Administration (FDA) as an adjuvant therapy in adult patients who have undergone complete gross resection of KIT-positive GIST.

scholarly journals How about Levetiracetam in Glioblastoma? An Institutional Experience and Meta-Analysis

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3770
Author(s):  
Ramazan Jabbarli ◽  
Yahya Ahmadipour ◽  
Laurèl Rauschenbach ◽  
Alejandro N. Santos ◽  
Marvin Darkwah Darkwah Oppong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multimodal Treatment ◽  
Controlled Trial ◽  
Meta Analysis ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Free Survival ◽  
Randomized Controlled ◽  
Prospective Randomized Controlled Trial ◽  
Institutional Experience

Despite multimodal treatment, the prognosis of patients with glioblastoma (GBM) remains poor. Previous studies showed conflicting results on the effect of antiepileptic drugs (AED) on GBM survival. We investigated the associations of different AED with overall survival (OS) and progression-free survival (PFS) in a large institutional GBM cohort (n = 872) treated January 2006 and December 2018. In addition, we performed a meta-analysis of previously published studies, including this study, to summarize the evidence on the value of AED for GBM prognosis. Of all perioperatively administered AED, only the use of levetiracetam (LEV) was associated with longer OS (median: 12.8 vs. 8.77 months, p < 0.0001) and PFS (7 vs. 4.5 months, p = 0.001). In the multivariable analysis, LEV was independently associated with longer OS (aHR = 0.74, p = 0.017) and PFS (aHR = 0.68, p = 0.008). In the meta-analysis with 5614 patients from the present and seven previously published studies, outcome benefit for OS (HR = 0.83, p = 0.02) and PFS (HR = 0.77, p = 0.02) in GBM individuals with LEV was confirmed. Perioperative treatment with LEV might improve the prognosis of GBM patients. We recommend a prospective randomized controlled trial addressing the efficacy of LEV in GBM treatment.

scholarly journals Glioblastoma and Increased Survival with Longer Chemotherapy Duration

2019 ◽  
Vol 12 (3) ◽  
pp. 65-69 ◽  
Author(s):  
Dory Abou Jaoude ◽  
Joseph A Moore ◽  
Matthew B Moore ◽  
Philip Twumasi-Ankrah ◽  
Elizabeth Ablah ◽  
...  
Keyword(s):  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Rank Test ◽  
Free Survival ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Optimal Duration ◽  
Multicenter Prospective Study ◽  
One Year

Introduction The five-year survival rate for patients with glioblastoma (GBM) is low at approximately 4.7%. Radiotherapy plus concomitant and adjuvant temozolomide (TMZ) remains the standard of care. The optimal duration of therapy with TMZ is unknown. This study sought to evaluate the survival benefit of two years of treatment. Methods This was a retrospective chart review of all patients diagnosed with GBM and treated with TMZ for up to two years between January 1, 2002 and December 31, 2011. The Kaplan-Meier method with log-rank test was used to estimate the progression-free survival (PFS) and the overall survival (OS). The results were compared to historical controls and data from previous clinical trials of patients treated up to one year. Results Data from 56 patients with confirmed GBM were evaluated. The OS probability was 54% (SE = 0.068) at one year, 28.3% (SE = 0.064) at two years, 17.8% (SE = 0.059) at three years, and 4% (SE = 0.041) at five years. Seven patients (12.5%) were treated with TMZ for two years. Their median time-to-progression was 28 months (95% CI = 5.0 - 28.0), and they had an increased survival probability at three years compared to other patients (log-rank test χ2 (1, N = 56) = 19.2, p < 0.0001). Conclusions There may be an advantage for a longer duration of TMZ therapy among patients with GBM, but the sample size was too small for generalization. A multicenter prospective study is needed to dentify optimal duration of TMZ therapy.

scholarly journals The impact of surgery in high grade gliomas - a literature review

2015 ◽  
Vol 29 (3) ◽  
pp. 295-308
Author(s):  
Adriana Baritchii ◽  
A. Gubian ◽  
St.I. Florian
Keyword(s):  
Malignant Gliomas ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
Cortical Mapping ◽  
High Grade ◽  
Free Survival ◽  
Mortality And Morbidity ◽  
High Grade Gliomas ◽  
The Impact ◽  
Related Mortality

Abstract Malignant gliomas are aggressive brain cancers. After many decades of intensive research they represent a major cause of cancer related mortality and morbidity. Management of malignant gliomas is very difficult. None of the current treatments are curative. High grade gliomas are optimally treated with surgery followed by radiotherapy and chemotherapy. The impact of surgery on progression free survival and overall survival was a constant preoccupation and debate for decades among neurosurgeons. Different studies published in the last 25 years have provided evidence that the extent of resection of high grade gliomas can influence time to progression and median survival, although so far there is no class I prospective randomized trial to fully answer this question. Some of the most important studies are reviewed here. The modern neurosurgery relay on some tools that proved to be very helpful in guiding the surgeon to achieve the maximal tumoral cytoreduction with minimum impact on the brain’s eloquent areas. iMRI has been proved to be safe and became an important tool during tumor surgery, used alone or in conjuction with other important techniques: intraoperative neurophysiology, awake cortical mapping, 5-ALA fluorescence etc. Although so far the prognostic of high grade gliomas is still disappointing, further understanding of the biology of these tumors and a patient-tailored treatment could be the keys of finding a cure in the future.

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