scholarly journals Treatment with Tumor-Treating Fields Therapy and Pulse Dose Bevacizumab in Patients with Bevacizumab-Refractory Recurrent Glioblastoma: A Case Series

2016 ◽  
Vol 8 (1) ◽  
pp. 1-9 ◽  
Author(s):  
George Ansstas ◽  
David D. Tran

Patients with bevacizumab-refractory recurrent glioblastoma multiforme (GBM) have a poor prognosis. We propose that instead of continuing on bevacizumab, patients should switch to treatment with Optune™, a novel antimitotic Tumor-Treating Fields (TTFields) therapy approved in the United States for newly diagnosed and recurrent GBM. This would reserve bevacizumab for subsequent disease progression. In this case series, we describe 8 patients with recurrent GBM who had disease progression on bevacizumab, discontinued bevacizumab treatment, and were treated with TTFields therapy alone. After subsequent radiographic or clinical progression, 5 patients were rechallenged with bevacizumab in a ‘pulse dose' fashion, an approach not previously described. Following treatment with TTFields therapy, median overall survival (OS) was 216 days (7.2 months). Median OS from last dose of initial bevacizumab was 237 days (7.9 months), twice that of historical controls for bevacizumab failures, and median OS from the first dose of bevacizumab rechallenge was 172 days (5.7 months). TTFields therapy was well tolerated, with a mean adherence rate of 74.2% (range, 48.2-92.9%). These results support the use of TTFields therapy with pulse dose bevacizumab as an option in patients with refractory GBM.

2020 ◽  
Vol 20 (1) ◽  
pp. 18-23
Author(s):  
Kyle P O’Connor ◽  
Ali H Palejwala ◽  
Camille K Milton ◽  
Victor M Lu ◽  
Chad A Glenn ◽  
...  

Abstract BACKGROUND Laser interstitial thermal therapy (LITT) is being used for the treatment of recurrent glioblastoma multiforme (GBM). Lesions can be treated using 1 or multiple LITT fibers depending on the preference of surgeons. Usually, more fibers are needed for coverage of larger tumors. OBJECTIVE To investigate and analyze how tumor size affected the number of LITT fibers used. METHODS This is a retrospective review of patients undergoing treatment of recurrent GBM. Patients were treated with up to 4 LITT fibers for adequate tumor coverage. Patient demographics, tumor characteristics, length of stay, complications, and biopsy results were recorded. RESULTS A total of 43 cases were treated using LITT, and of these cases, 31 consisted of contiguous lesions. We used more fibers to treat larger tumor volumes. On average, for each 5 cc of tumor volume, a fiber was added for proper coverage (P = .554). Complications and length of stay were similar across the groups (P = .378, P = .941). CONCLUSION LITT can be used for the treatment of recurrent GBM. For each 5 cc of tumor volume, a LITT fiber can be added to the treatment plan.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii44-ii45
Author(s):  
Lawrence Cher ◽  
Anna Nowak ◽  
George Iatropoulos ◽  
Samantha Bowyer ◽  
Hui Gan ◽  
...  

Abstract The VEGF pathway remains an important target in GBM given its vascularity and autocrine VEGF signalling. Olinvacimab (TTAC-0001) is a fully humanised VEGFR2 Mab that binds and inhibits the receptor. This report assesses the safety, dosing schedules and efficacy of Olinvacimab in recurrent GBM. We conducted a two-site, 3 arm, open-label study of Olinvacimab in recurrent GBM. Eligible patients were ≥18 years with RANO-measurable lesion, KPS ≥ 80, and had completed chemoradiotherapy without prior bevacizumab therapy. We assessed three arms, 8 mg/kg and 12mg/kg weekly for 3 of every 4 weeks, and 12 mg/kg weekly. Three patients were treated in arms 1 and 2 and 6 in arm 3. Safety assessments were performed prior to dose escalation. The main toxicity was development of grade 1 (67%) and 2 (8%%) cutaneous haemangiomas. Common toxicities seen with other VEGF directed therapies, including hypertension, impaired wound healing, and proteinuria were not seen in this cohort. Efficacy was assessed by MRI using RANO criteria. 6 month PFS was 17%, with disease control in 25%, with steroid dose reduction. The longest response was 15 months. On DCE MRI, there was no significant difference in perfusion parameters between baseline and 1st follow-up MRI comparing those with SD and PD. However, 6 of 12 patients showed decreased Ktrans > 20 % of baseline, consistent with an anti-angiogenic effect of Olinvacimab. Pharmacokinetics showed a decreased clearance rate and increased half-life of Olinvacimab compared to the prior Phase I study. Pharmacodynamic studies showed significantly higher levels of angiogenic markers, particularly VEGF-A in those treated at 12mg/kg vs arm 1. VEGF-A, C and D levels were elevated in patients with SD compared to those with PD. Conclusion: Olinvacimab was well tolerated with a different toxicity profile to other VEGFR directed therapies. There were promising responses in 25% of patients.


2009 ◽  
Vol 27 (12) ◽  
pp. 2052-2058 ◽  
Author(s):  
Evanthia Galanis ◽  
Kurt A. Jaeckle ◽  
Matthew J. Maurer ◽  
Joel M. Reid ◽  
Matthew M. Ames ◽  
...  

PurposeVorinostat, a histone deacetylase inhibitor, represents a rational therapeutic target in glioblastoma multiforme (GBM).Patients and MethodsPatients with recurrent GBM who had received one or fewer chemotherapy regimens for progressive disease were eligible. Vorinostat was administered at a dose of 200 mg orally twice a day for 14 days, followed by a 7-day rest period.ResultsA total of 66 patients were treated. Grade 3 or worse nonhematologic toxicity occurred in 26% of patients and consisted mainly of fatigue (17%), dehydration (6%), and hypernatremia (5%); grade 3 or worse hematologic toxicity occurred in 26% of patients and consisted mainly of thrombocytopenia (22%). Pharmacokinetic analysis showed lower vorinostat maximum concentration and area under the curve (0 to 24 hours) values in patients treated with enzyme-inducing anticonvulsants, although this did not reach statistical significance. The trial met the prospectively defined primary efficacy end point, with nine of the first 52 patients being progression-free at 6 months. Median overall survival from study entry was 5.7 months (range, 0.7 to 28+ months). Immunohistochemical analysis performed in paired baseline and post-vorinostat treatment samples in a separate surgical subgroup of five patients with recurrent GBM showed post treatment increase in acetylation of histones H2B and H4 (four of five patients) and of histone H3 (three of five patients). Microarray RNA analysis in the same samples showed changes in genes regulated by vorinostat, such as upregulation of E-cadherin (P = .02).ConclusionVorinostat monotherapy is well tolerated in patients with recurrent GBM and has modest single-agent activity. Histone acetylation analysis and RNA expression profiling indicate that vorinostat in this dose and schedule affects target pathways in GBM. Additional testing of vorinostat in combination regimens is warranted.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1558-1558 ◽  
Author(s):  
J. Sadones ◽  
C. Chaskis ◽  
E. J. Joosens ◽  
L. A. Dhondt ◽  
J. Baurain ◽  
...  

1558 Background: The Epidermal Growth Factor Receptor (EGFR) gene is frequently amplified and mutated in high-grade gliomas. We are investigating the activity of the EGFR-targeted monoclonal antibody cetuximab for the treatment of patients (pts) with recurrent glioblastoma multiforme (GBM) following surgery, radiotherapy and chemotherapy. Methods: Adult pts with recurrent GBM are allocated to two parallel treatment strata according to the amplification status of the EGFR gene (determined by FISH). According to a Simon two-stage phase II study design 1 response in 13 pts/stratum is required to continue recruitment and complete the second stage of pt recruitment. Cetuximab is administered at 400 mg/m2 (2 hour infusion) day 1 and 250 mg/m2 day 8 and for all subsequent weekly doses (1 hour infusion). Results: Between May and December 2005, 17 pts were recruited (10 without EGFR-ampl, 4 with EGFR-ampl and 3 under investigation); 4F/13M; median age 51 years, range 32–67). Recruitment is ongoing. Sixteen pts initiated study treatment; 1 pt withdrew consent before the initiation of therapy. Treatment related toxicity in the first 94 treatment cycles consisted of grade 1/2 folliculitis/dermitis in all treated pts. Grade 3 adverse events consisted of thrombocytopenia (n=1 pt), diminished consciousness (n=1 pt), dizziness/confusion (n=1 pt), infectious bronchopneumonia (n=1 pt), and infectious cellulitis (n=1 pt). Thirteen pts have been evaluated for response ≤ week 8 of study treatment. Eleven pts had progression of disease. Two patients had SD at 8 weeks (follow-up is ongoing). Conclusions: These preliminary data suggest that cetuximab can be safely administered to pretreated patients with recurrent GBM. Updated results regarding safety and activity as well as a correlative study of EGFR and PTEN expression and gene copy number of the GBM and response to cetuximab will be presented at the meeting. No significant financial relationships to disclose.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2027-2027 ◽  
Author(s):  
S. Sathornsumetee ◽  
J. N. Rich ◽  
J. J. Vredenburgh ◽  
A. Desjardins ◽  
J. A. Quinn ◽  
...  

2027 Background: Recent studies have demonstrated promising anti-glioma activity of imatinib mesylate (IM) and hydroxyurea (H). Angiogenesis is one of the hallmarks of GBM with VEGF as a key regulator. This study attempts to extend the efficacy of IM and H by adding a VEGF receptor inhibitor, vatalanib (V; PTK787/ZK22584). Methods: We employ a ‘3+3‘ dose escalation design to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of IM and V when administered with fixed dose of H in adult recurrent GBM patients with < 3 prior recurrences, KPS = 70% and adequate organ function. Patients are stratified based on concurrent enzyme-inducing anticonvulsant (EIAC) administration, and both strata (A- not on EIAC and B- on EIAC) are independently dose-escalated. Initial dose levels for stratum A: IM - 400 mg/day; H - 500 mg bid; V- 250 mg bid and for stratum B: IM- 500 bid; H-500 mg bid; V- 500 mg bid. Patients are given only V on day 1–7 of cycle 1 and then IM+H+V daily thereafter. Only cycle 1 is 35 days with subsequent cycles of 28 days. Response is evaluated every other cycle. Pharmacokinetic (PK) studies are performed on days 7 and 35 of cycle 1. Results: Thirty-five recurrent GBM patients have enrolled. The median age is 51.5 (range 31 to 75), 66% are male, and 51% are on EIAC. One DLT (grade 3 thrombocytopenia) occurred in a stratum A patient on dose level three . For stratum B, two DLTs (grade 3 hypertension and ALT elevation) occurred in a patient on dose level two and one DLT (grade 3 fatigue) occurred in a patient on dose level three. MTDs for each stratum have not been reached and accrual is ongoing. PK results are pending. Ten partial responses (29%) have been observed and nine patients remain on study including three who have received more than 6 cycles of therapy. Conclusions: Combination of imatinib, hydroxyurea and vatalanib is safe and well-tolerated with an encouraging rate of radiographic response. Further accrual is in progress to define the MTD. No significant financial relationships to disclose.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13538-e13538
Author(s):  
Marc C. Chamberlain ◽  
Bryan T. Kim

e13538 Objective: A single institution retrospective evaluation of nivolumab following disease progression on bevacizumab in adults with recurrent glioblastoma (GBM) with an objective of determining progression free survival (PFS). Background: There is no accepted therapy for recurrent GBM after failure of bevacizumab. Methods: 16 adults, ages 52-72 years (median 62), with recurrent GBM were treated. All patients had previously been treated with surgery, concurrent radiotherapy and temozolomide, and post-radiotherapy temozolomide. Bevacizumab (with or without lomustine) was administered to all patients at first recurrence. Patients were treated with nivolumab only (3mg/kg) once every 2 weeks at second recurrence. One cycle of nivolumab was defined as 2 treatments. Neurological evaluation was performed bi-weekly and neuroradiographic assessment every 4 weeks. Results: A total of 37 treatment cycles (median 2) were administered of nivolumab in which there were 14 Grade 2 adverse events (AEs) and Grade 3 AEs in 2 patients. No Grade 4 or 5 AEs were seen. Following 1 month of nivolumab, 7 patients’ demonstrated progressive disease and discontinued therapy. No patient demonstrated a response though 9 patients demonstrated neuroradiographic stable response. Survival in the entire cohort ranged from 2 - 6 months with a median of 3.5 months (CI: 2.8, 4.2). Median and 6-month PFS at 6 months was 2.0 months (range 1-5 months; CI: 1.3, 2.7) and 0% respectively. Conclusions: Nivolumab salvage therapy demonstrated no survival advantage in patients with recurrent bevacizumab refractory GBM emphasizing a continued unmet need in neuro-oncology.


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S334-S335
Author(s):  
Natasha E Hongsermeier-Graves ◽  
Rohan Khazanchi ◽  
Nada Fadul

Abstract Background It is well known that the HIV epidemic and COVID-19 pandemic have both disproportionately harmed marginalized minority and immigrant communities in the United States. The risk factors associated with disease incidence and outcomes reaffirm that structural vulnerabilities—sociopolitically imposed risk factors like discrimination, legal status, poverty, and beyond which impact a patient’s opportunity to achieve optimal health—play a key role in facilitating the inequitable harms of COVID-19 and HIV alike. This study explores the role of structural forces in increasing the risk of SARS-CoV-2 coinfection among people with HIV (PWH). Methods We performed a retrospective chart review of PWH receiving care at the University of Nebraska Medical Center HIV clinic in Omaha, Nebraska, to collect patient demographics, comorbidities, HIV outcomes, and COVID-19 outcomes for 37 patients with HIV and SARS-CoV-2 coinfection as of August 27, 2020. As a comparison group, we obtained demographic data from a registry of all patients seen at the HIV clinic. We used R Statistical Software to perform descriptive statistical analysis. Results Relative to our overall HIV clinic population, over twice as many Hispanic patients (35.1% vs. 16.0%), three times as many undocumented patients (13.5% vs. 4.2%), and four times as many refugee patients (16.2% vs. 4.0%) had COVID-19. The majority (67.6%) of coinfected patients reported working in “essential” jobs during the pandemic. Thirty-four of the 37 people with HIV and COVID-19 (PWHC) had at least one comorbidity, including increased BMI (83.7%), hypertension (64.9%), or hyperlipidemia (48.6%). All 37 PWHC remained alive as of October 4, 2020. Demographics and HIV Disease Progression of People with HIV and SARS-CoV-2 Coinfection vs. Overall HIV Clinic Registry Demographics and HIV Disease Progression of People with HIV and SARS-CoV-2 Coinfection vs. Overall HIV Clinic Registry (continued) Conclusion The disproportionate burden of SARS-CoV-2 coinfection on Hispanic, undocumented, and refugee PWH may be a product of structural vulnerabilities contributing to greater risk of exposure. Although all 37 PWHC had well-controlled HIV and relatively mild COVID-19 courses, the broader theme of disproportionate COVID-19 incidence among vulnerable sub-populations of people with HIV reaffirms the importance of structural interventions to mitigate current and downstream harms. Disclosures All Authors: No reported disclosures


2000 ◽  
Vol 18 (7) ◽  
pp. 1481-1491 ◽  
Author(s):  
D. Osoba ◽  
M. Brada ◽  
W.K. A. Yung ◽  
M. Prados

PURPOSE: To determine whether chemotherapy with temozolomide (TMZ) versus procarbazine (PCB) for recurrent glioblastoma multiforme (GBM) was associated with improvement in health-related quality of life (HRQOL). PATIENTS AND METHODS: HRQOL was assessed at baseline and during treatment using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and a Brain Cancer Module (BCM20) in two clinical trials that enrolled a total of 366 patients. Two hundred eighty-eight patients provided HRQOL data that could be used for analysis; 109 patients received TMZ in a phase II study, whereas 89 patients received TMZ and 90 received PCB in a randomized phase III study. Changes from baseline in the scores of seven preselected HRQOL domains (role and social functioning, global quality of life [QOL], visual disorders, motor dysfunction, communication deficit, and drowsiness) were calculated for all groups. Statistical significance, effect sizes, and proportions of patients with improved HRQOL scores (changes of ≥ 10 points) were calculated. RESULTS: Before disease progression, patients treated with TMZ were found to have an improvement in most of the preselected HRQOL domain scores compared with their baseline (pretreatment) scores. Those who were progression-free on TMZ at 6 months had improvement in all the preselected HRQOL domains. Conversely, patients treated with PCB reported deterioration in HRQOL that was independent of whether or not the disease had progressed by 6 months. Patients with disease progression, regardless of treatment, experienced a sharp decline in all domains at the time of progression. CONCLUSION: Treatment with TMZ was associated with improvement in HRQOL scores compared with treatment with PCB. The deterioration reported by PCB-treated patients was likely because of toxicity. Delaying disease progression by treatment with TMZ is beneficial to the HRQOL status of patients with recurrent GBM.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS2102-TPS2102 ◽  
Author(s):  
Andrew Jacob Brenner ◽  
Yael Cohen ◽  
James J Vredenburgh ◽  
Katherine B. Peters ◽  
Eyal Breitbart ◽  
...  

TPS2102 Background: VB-111 is an anti-angiogenic agent consisting of a non-replicating adenovirus vector (Ad-5) with a modified murine pre-proendothelin promoter leading to apoptosis of tumor vasculature by expressing a fas-chimera transgene in angiogenic endothelial cells. In a phase I/II dose-escalation study, safety and efficacy of VB-111 in patients with recurrent Glioblastoma Multiforme (GBM) were evaluated. Methods: VB-111 was administered as a single intravenous infusion at escalating doses from 1x1012 to 3x1012 viral particles (VPs), followed by repeat doses of 3x1012 or 1x1013every 2 months. Assessments included safety, pharmacokinetics, tumor response (RANO criteria) and overall survival (OS). Results: Twenty eight patients aged 26 – 74 years at 3 medical centers in the US received up to 8 repeat doses of VB-111. The median OS was 360 [range: 70-574] and 266 days [range: 28-664] for patients receiving at least one dose of 1x1013VPs (high dose) vs. subjects who received lower doses, respectively (p NS). Progression free survival was 87 vs 55 days for patients who received high dose and for lower doses, respectively (p = 0.01). Median follow-up was 232 days. Three patients had a partial response (PR) at 82, 86 and 408 days post initial VB-111 dosing. Twenty one of the patients who progressed on VB-111 treatment received bevacizumab off study; 7 of the 15 evaluable patients (47%) had a PR compared to 30% expected according to literature. VB-111 was safe and well tolerated, 53 adverse events were reported, 14 were classified as possibly related to VB-111. All events were of CTCAE grade 1-2 except one grade 3 pulmonary embolism. There were no study related deaths. One patient developed peri-tumoral edema, which resolved with corticosteroid therapy. Events occurring in > 10% of the patients included headache and fatigue. Conclusions: VB-111 was safe and well tolerated in patients with recurrent GBM with repeat doses of up to 1x1013 VPs. Tumor responses were seen. Overall survival was about 3 months longer than historical data in recurrent GBM, including standard of care anti-angiogenic agents. Data suggests that VB-111 potentiates the response to bevacizumab given at further progression. Clinical trial information: NCT01260506.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13000-e13000
Author(s):  
Eluska Iruarrizaga ◽  
Eider Azkona ◽  
Unai Aresti ◽  
Itziar Rubio ◽  
Mikel Arruti ◽  
...  

e13000 Background: Glioblastoma multiforme constitutes the most common and malignant form of primary brain tumor. Median survival for recurrent disease is 3-9 months. Combining bevacizumab with irinotecan represents an option of treatment in recurrent GBM. Methods: We performed a retrospective review of patients with recurrent GBM treated with bevacizumab (10 mg/kg) and irinotecan (340 mg/m2 for patients receiving enzyme-inducing antiepileptic drugs –EIAEDs- and 125 mg/m2 for patients not receiving EIAEDs) every 14 days on a 4-week cycle. Inclusion criteria: age ≥ 18, histology of GBM, progression after radiotherapy and temozolomide and signed informed consent for bevacizumab compassionate use. MRI-FLAIR sequence was used every 8 weeks to assess response. Results: From October 2009 to December 2012, a total of 26 patients were included; 15 (57.7%) male/11 (42.3%) female. Median age of the patients was 52 years (32-69); ECOG 0/1/2/3: 7.7/46.2/38.5/7.7% respectively; 19.23 % of patients received EIAEDs. Median number of cycles was 2.5 (1-14). Response rate was 30.8% (23.1% PR; 7.7 % CR); SD 23.1 %. Median PFS was 23 weeks; median OS was 30 weeks. Most common grade 3 toxicities were: asthenia 26.9%, arthromyalgia 3.8%, diarrhea 3.8% and hepatotoxicity 15.4%; grade 2 thromboembolic complications: 3.8 %. Conclusions: Combination of bevacizumab and irinotecan is effective against recurrent GBM and prolongs PFS and OS compared with historical controls, with mild toxicity.


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