June 2010
Neuroscience News Network is a monthly e-newsletter published by the National Brain Tumor Society's Patient Services Department to share events, news, and research articles with health professionals in the brain tumor community.
In this edition:
- Living With a Brain Tumor Conference in Dallas-Ft. Worth Are in October 2010
- My.BrainTumorCommunity.Org Discussion Forums
- Phase I/IIa Study of Cilengitide and Temozolomide With Concomitant Radiotherapy Followed by Cilengitide and Temozolomide Maintenance Therapy in Patients With Newly Diagnosed Glioblastoma
- Lack of Efficacy of Bevacizumab Plus Irinotecan in Children With Recurrent Malignant Glioma and Diffuse Brainstem Glioma: A Pediatric Brain Tumor Consortium Study
- Continuous Low-Dose Temozolomide and Celecoxib in Recurrent Glioblastoma
1. Living With a Brain Tumor Conference in Dallas-Ft. Worth Area in October 2010
Join National Brain Tumor Society on October 8-9, 2010 for an exciting conference created for patients, survivors, and their families. Saturday will feature presentations from multidisciplinary health professionals on topics ranging from treatment updates, survivorship, quality of life, pediatric tumors, and more. The conference will also provide opportunities for patients and families to receive support and connect with others with two tracks specifically tailored to adult and pediatric patients and families. For more information for you patients and their families, visit our website.
2. My.BrainTumorCommunity.Org Discussion Forums
This new online community for brain tumor patients and their families offers a way to connect with others 24 hours a day, 7 days a week. The discussion forums have topics for patients to connect and share with each other on specific information including tumor types, caregiving, end of life, young adult survivorship, and so much more. Share the new online community with your patients today!
3. Phase I/IIa Study of Cilengitide and Temozolomide With Concomitant Radiotherapy Followed by Cilengitide and Temozolomide Maintenance Therapy in Patients With Newly Diagnosed Glioblastoma
Roger Stupp, Monika E. Hegi, Bart Neyns, Roland Goldbrunner, Uwe Schlegel, Paul M.J. Clement, Gerhard G. Grabenbauer, Adrian F. Ochsenbein, Matthias Simon, Pierre-Yves Dietrich, Torsten Pietsch, Christine Hicking, Joerg-Christian Tonn, Annie-Claire Diserens, Alessia Pica, Mirjam Hermisson, Stefan Krueger, Martin Picard, Michael Weller
Invasion and migration are key processes of glioblastoma and are tightly linked to tumor recurrence. Integrin inhibition using cilengitide has shown synergy with chemotherapy and radiotherapy in vitro and promising activity in recurrent glioblastoma. This multicenter, phase I/IIa study investigated the efficacy and safety of cilengitide in combination with standard chemoradiotherapy in newly diagnosed glioblastoma.
Patients (age 18 to 70 years) were treated with cilengitide (500 mg) administered twice weekly intravenously in addition to standard radiotherapy with concomitant and adjuvant temozolomide. Treatment was continued until disease progression or for up to 35 weeks. The primary end point was progression-free survival (PFS) at 6 months.
Fifty-two patients (median age, 57 years; 62% male) were included. Six- and 12-month PFS rates were 69% (95% CI, 54% to 80%) and 33% (95% CI, 21% to 46%). Median PFS was 8 months (95% CI, 6.0 to 10.7 months). Twelve- and 24-month overall survival (OS) rates were 68% (95% CI, 53% to 79%) and 35% (95% CI, 22% to 48%). Median OS was 16.1 months (95% CI, 13.1 to 23.2 months). PFS and OS were longer in patients with tumors with O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation (13.4 and 23.2 months) versus those without MGMT promoter methylation (3.4 and 13.1 months). The combination of cilengitide with temozolomide and radiotherapy was well tolerated, with no additional toxicity. No pharmacokinetic interactions between temozolomide and cilengitide were identified.
Compared with historical controls, the addition of concomitant and adjuvant cilengitide to standard chemoradiotherapy demonstrated promising activity in patients with glioblastoma with MGMT promoter methylation.
Source information:
Journal of Clinical Oncology, JCO Early Release, published online ahead of print May 3 2010, 10.1200/JCO.2009.26.6650A.
4. Lack of Efficacy of Bevacizumab Plus Irinotecan in Children With Recurrent Malignant Glioma and Diffuse Brainstem Glioma: A Pediatric Brain Tumor Consortium Study
Sridharan Gururangan, Susan N. Chi, Tina Young Poussaint, Arzu Onar-Thomas, Richard J. Gilbertson, Sridhar Vajapeyam, Henry S. Friedman, Roger J. Packer, Brian N. Rood, James M. Boyett, Larry E. Kun
A phase II study of bevacizumab (BVZ) plus irinotecan (CPT-11) was conducted in children with recurrent malignant glioma (MG) and intrinsic brainstem glioma (BSG).
Eligible patients received two doses of BVZ intravenously (10 mg/kg) 2 weeks apart and then BVZ plus CPT-11 every 2 weeks until progressive disease, unacceptable toxicity, or a maximum of 2 years of therapy. Correlative studies included diffusion weighted and T1 dynamic contrast - enhanced permeability imaging, BVZ pharmacokinetics, and estimation of vascular endothelial growth factor receptor 2 (VEGFR-2) phosphorylation in peripheral blood mononuclear cells (PBMC) after single-agent BVZ.
Thirty-one evaluable patients received a median of two courses of BVZ plus CPT-11 (range, 1 to 19). No sustained responses were observed in either stratum. Median time to progression for all 34 eligible patients enrolled was 127 days for MG and 71 days for BSG. Progression-free survival rates at 6 months were 41.8% and 9.7% for MG and BSG, respectively. Toxicities related to BVZ included grade 1 to 3 fatigue in seven patients, grade 1 to 2 hypertension in seven patients, grade 1 CNS hemorrhage in four patients, and grade 4 CNS ischemia in two patients. The mean diffusion ratio decreased after two doses of BVZ in patients with MG only. Vascular permeability parameters did not change significantly after therapy in either stratum. Inhibition of VEGFR-2 phosphorylation in PBMC was detected in eight of 11 patients after BVZ exposure.
BVZ plus CPT-11 was well-tolerated but had minimal efficacy in children with recurrent malignant glioma and brainstem glioma.
Source information:
Journal of Clinical Oncology,Early Release, published online ahead of print May 17 2010,10.1200/JCO.2009.26.8789.
5. Continuous Low-Dose Temozolomide and Celecoxib in Recurrent Glioblastoma
Stockhammer F, Misch M, Koch A, Czabanka M, Plotkin M, Blechschmidt C, Tuettenberg J, Vajkoczy P.
Patients with recurrent primary GBM treated with POH survived significantly longer (log rank test, P < 0.0001) than untreated group. Patients with recurrent primary GBM in deep location survived significantly longer than with lobar location (log rank test, P < 0.0001). Median survival rate of secondary GBM was 11.2 months, longer (log rank test, P = 0.0366) than primary GBM (5.9 months). Radiographic improvement and reduction of corticosteroid dosage (36%) further associated with a delay towards progression.Even after gross tumor resection and combined radiochemotherapy, glioblastomas recur within a few months. Salvage therapy often consists of rechallenging with temozolomide in a dose-intensified schedule.
Previously, low-dose metronomic temozolomide in combination with cyclo-oxigenase 2 inhibitors has had a beneficial effect as first-line treatment for glioblastoma. We report our experience with this procedure in recurrent glioblastomas after standard treatment. From June 2007 to April 2009, 28 patients with recurrent glioblastoma received continuous low-dose temozolomide of 10 mg/m(2) twice daily and 200 mg celecoxib. Before therapy the recurrent tumor was resected in 19 of 28 patients. Microvessel density (MVD) was determined by immunohistochemistry in 19 patients, and MGMT promoter methylation status, using the pyrosequencing method, was determined in 17 patients. In 14/28 patients, positron emission tomography with [F-18]-fluoroethyl)-L: -tyrosine (FET-PET) was performed. Tumor progression was defined by the Macdonald criteria on MRI every 8-12 weeks or by clinical deterioration. The median time to progression was 4.2 months.
Progression-free survival (PFS) after 6 months was 43%. Except for a lymphopenia in one patient, there was no grade 3 or 4 toxicity. PFS did not correlate with MVD or MGMT status. A high FET uptake correlated with tumor control after 6 months under therapy (P = 0.041, t-test). Low-dose continuous temozolomide in combination with celecoxib seems to have activity in recurrent glioblastoma without relevant toxicity. High FET uptake correlated with a better outcome under metronomic therapy.
Source information:
J Neurooncol. May 6, 2010 PMID: 20446016.
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