Author: "T. Cloughesy" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"T. Cloughesy"' showing total 164 results

Start Over Author "T. Cloughesy"

164 results on '"T. Cloughesy"'

1. The CNS-penetrant EGFR inhibitor, ERAS-801, shows promising nonclinical activity in a CNS metastases model of EGFR mutant NSCLC

Author: J. Tsang, E. Zhao, R. Plawat, T. Cloughesy, and D. Nathanson
Subjects: Cancer Research, Oncology
Published: 2022
Full Text: View/download PDF

2. P11.65.B GBM AGILE: A global, phase 2/3 adaptive platform trial to evaluate multiple treatment regimens in newly diagnosed and recurrent glioblastoma

Author: M Weller, B Ellingson, B Alexander, P Wen, E Sulman, H Colman, D Berry, K Tanner, M Khasraw, M Lim, J Perry, A Lassman, T Cloughesy, W K A Yung, E Q Lee, I Mellinghoff, G Gordon, J de Groot, T Mikkelsen, W Cavenee, A Nelli, M Buxton, and W Li
Subjects: Cancer Research, Oncology, Neurology (clinical)
Abstract: Background GBM AGILE (Glioblastoma Adaptive, Global, Innovative Learning Environment) is a biomarker based, multi-arm, international, seamless Phase 2/3 Response Adaptive Randomization platform trial designed to rapidly identify experimental therapies that improve overall survival and confirm efficacious experimental therapies and associated biomarker signatures to support new drug approvals and registration. It is a collaboration between academic investigators, patient organizations and industry, under the sponsorship of the non-profit organization, Global Coalition for Adaptive Research, to support new drug applications for newly diagnosed and recurrent GBM. Material and Methods The primary objective of GBM AGILE is to identify therapies that effectively improve overall survival in patients with newly diagnosed or recurrent GBM. Bayesian response adaptive randomization is used within subtypes of the disease to assign participants to investigational arms based on their performance. Operating under a master protocol, GBM AGILE allows multiple drugs from different pharmaceutical companies to be evaluated simultaneously and/or over time against a common control arm. Based on performance, a drug may graduate and move to a Stage 2 (Phase 3) within the trial, and the totality of the data can be used for a new drug application and registration process. New experimental therapies are added as information about promising new drugs is identified while other therapies are removed as they complete their evaluation. The master protocol/ trial infrastructure includes efficiencies through an adaptive trial design, shared control arm and operational processes such as risk-based monitoring and enhanced remote activities. With its adaptable structure, GBM AGILE has continued trial activation, inclusion of new investigational therapies, and enrollment globally through the challenges of a global pandemic.GBM AGILE provides an efficient mechanism to screen and develop robust information regarding the efficacy of proposed novel therapeutics and associated biomarkers for GBM and to quickly move therapies and biomarkers into clinic. GBM AGILE received initial approval from the United States FDA in April 2019, and in Europe through the Voluntary Harmonization Procedure (VHP) in April, 2021. As of 2022, AGILE has screened over 1000 patients studying multiple investigational treatments. Enrollment rates are 3 to 4 times greater than traditional GBM trials, with active sites averaging 0.75 to 1 patients/site/month. Currently, there are 41 sites activated in the US, 4 in Canada and 2 in Switzerland and an estimated 24 sites yet to open in Germany, France, Switzerland, Italy and Austria. In addition to the continued expansion in Europe, effort is undergoing to extend the trial to China and Australia as well. Clinical trial information: NCT03970447
Published: 2022
Full Text: View/download PDF

3. 280O Pharmacokinetics and pharmacodynamics of paxalisib in newly diagnosed glioblastoma patients with unmethylated MGMT promoter status: Final phase II study results

Author: P. Wen, J.F. de Groot, J. Battiste, S. Goldlust, D. Damek, B. Ellingson, J. Garner, J. Friend, J. Simpson, A. Olivero, and T. Cloughesy
Subjects: Oncology, Hematology
Published: 2022
Full Text: View/download PDF

4. OS10.6 Infigratinib (BGJ398) in patients with recurrent gliomas with fibroblast growth factor receptor (FGFR) alterations: a multicenter phase II study

Author: Morris D. Groves, J. Raizer, F.Y.F.L. De Vos, Patrick Roth, Andrew B. Lassman, K Steward, J M Gil-Gil, Vinay K. Puduvalli, Paul Clement, Juan M. Sepúlveda-Sánchez, T. Cloughesy, N. Butowski, C Belda-Iniesta, Y Ye, Patrick Y. Wen, and S Moran
Subjects: Cancer Research, Mutation, business.industry, Phases of clinical research, Chromosomal translocation, medicine.disease, medicine.disease_cause, Fusion gene, Oncology, Fibroblast growth factor receptor, Glioma, medicine, Cancer research, Oral Presentations, In patient, Neurology (clinical), Progression-free survival, business
Abstract: BACKGROUND FGFR mutations and translocations occur in approximately 10% of glioblastomas (GBMs). FGFR3-TACC3 fusion has been reported as predictive of response to FGFR tyrosine kinase inhibitor therapy both pre-clinically and clinically. Infigratinib (BGJ398) is a selective small-molecule pan-FGFR kinase inhibitor that has demonstrated anti-tumor activity in several solid tumors with FGFR genetic alterations. Therefore, we conducted a phase II trial to test the efficacy of infigratinib in FGFR-altered recurrent GBM (NCT01975701). METHODS This open-label trial accrued adults with recurrent high-grade gliomas following failure of initial therapy that harbored FGFR1-TACC1 or FGFR3-TACC3 fusions; activating mutations in FGFR1, 2 or 3; or FGFR1, 2, 3, or 4 amplification. Oral infigratinib was administered 125 mg on days 1–21 every 28 days. Prophylaxis for hyperphosphatemia, a common toxicity, was recommended. The primary endpoint was the 6-month progression-free survival (6mPFS) rate by RANO (locally assessed, estimated by K-M method), with a goal of >40%. RESULTS As of the Sep 2017 data cut-off, 26 patients (16 men, 10 women; median age 55 years, range 20–76 years; 50% with ≥2 prior regimens) were treated, and 24 (92.3%) discontinued for disease progression (n=21) or other reasons (n=3). All patients had FGFR1 or FGFR3 gene alterations, and 4 had >1 gene alteration. The estimated 6mPFS rate was 16% (95% CI 5.0–32.5%); median PFS was 1.7 months (95% CI 1.1–2.8 months); median OS was 6.7 months (95% CI 4.2–11.7 months); ORR was 7.7% (95% CI 1.0–25.1%). The best overall response was: partial response 7.7% (FGFR1 mutation n=1; FGFR3 amplification n=1); stable disease 26.9%; progressive disease 50.0%; missing/unknown 15.3%. The most common (>15%) all-grade treatment-related adverse events (AEs) were hyperphosphatemia, fatigue, diarrhea, hyperlipasemia, and stomatitis. There were no grade 4 treatment-related AEs. Eleven patients (42.3%) had treatment-related AEs requiring dose interruptions or reductions (most commonly hyperphosphatemia). CONCLUSIONS Infigratinib induced partial response or stable disease in approximately one-third of patients with recurrent GBM and/or other glioma subtypes harboring FGFR alterations. Most AEs were reversible and manageable. Further potential combinations are being explored in patients with proven FGFR-TACC fusion genes and analysis of biomarker data is ongoing.
Published: 2019

5. P01.032 Associations of anticoagulant use with outcome in newly diagnosed glioblastoma

Author: Michael Weller, O Chinot, T. Cloughesy, David A. Reardon, Roger Stupp, Thierry Gorlia, Louis B. Nabors, E Le Rhun, Wolfgang Wick, and Els Genbrugge
Subjects: Oncology, Cancer Research, medicine.medical_specialty, business.industry, Newly diagnosed, medicine.disease, Outcome (game theory), Poster Presentations, Internal medicine, Medicine, Anticoagulant use, Neurology (clinical), business, Glioblastoma
Abstract: BACKGROUND: To test the hypothesis that, despite bleeding risk, anticoagulants improve outcome in glioblastoma because of reduced incidence of venous thromboembolic events and modulation of angiogenesis, infiltration and invasion. MATERIAL AND METHODS: We assessed survival associations of anticoagulant use from baseline up to start of temozolomide chemoradiotherapy (TMZ/RT) (period I) and from there to the start of maintenance TMZ chemotherapy (period II) by pooling data of three randomized clinical trials in newly diagnosed glioblastoma including 1,273 patients. Progression-free survival (PFS) and overall survival (OS) were compared between patients with: anticoagulant use versus no use; therapeutic versus prophylactic versus no use; different durations of anticoagulant use versus no use; anticoagulant use versus use of anti-platelet agents, versus neither nor. Cox regression models were stratified by trial and adjusted for baseline prognostic factors. RESULTS: Anticoagulant use was documented in 75 patients (5.9%) in period I and in 104 patients (10.2%) in period II. Anticoagulant use during period II, but not period I, was associated with inferior OS compared to no use on multivariate analysis (p=0.001, HR=1.52, 95% CI: 1.18–1.95). No decrease in OS became apparent when only patients with prophylactic anticoagulant use were considered. No survival association was established for anti-platelet agent use. CONCLUSION: Anticoagulant use was not associated with improved OS. Anticoagulants may not exert relevant anti-tumor properties in glioblastoma.
Published: 2018

6. OS09.6 Long-term follow-up data from 126 patients with recurrent high grade glioma from three Phase 1 trials of Toca 511 and Toca FC: Update and justification for a Phase 2/3 trial

Author: Michael A. Vogelbaum, David Piccioni, Bradley Elder, Steven N. Kalkanis, Jonathan Engh, T. Cloughesy, George J. Kaptain, Manish K. Aghi, Joseph Landolfi, and D. Bota
Subjects: Cancer Research, medicine.medical_specialty, business.industry, Long term follow up, Oncology and Carcinogenesis, Neurosciences, ORAL PRESENTATIONS, MICROBIOLOGY PROCEDURES, Oncology, Physical therapy, medicine, Neurology (clinical), Oncology & Carcinogenesis, Nuclear medicine, business, High-Grade Glioma
Abstract: Toca 511 (vocimagene amiretrorepvec) is an investigational, conditionally lytic, retroviral replicating vector. The vector infects human cells with selectivity for cancer cells because genome integration is dependent on cell division and viral replication is inhibited by innate and adaptive immune responses, defective in malignant tissues. Toca 511 spreads through cancer cells and stably delivers the gene for an optimized yeast cytosine deaminase that converts courses of the prodrug Toca FC (an investigational, extended-release version of 5-fluorocytosine) into 5-fluorouracil (5-FU). The combined treatment is designed to generate 5-FU in the tumor micro-environment, directly killing cancer cells, leading to activation of antigen presenting cells. 5-FU can also diffuse into nearby immunosuppressive myeloid cells and kill them, leading to further activation of the immune system against the tumor by removing important brakes on the lymphocytes. The safety, viral kinetics, immune response, and preliminary efficacy of Toca 511 and Toca FC have been investigated clinically since 2010 in three, open-label, ascending dose, Phase 1 studies of 126 treated patients with recurrent high grade glioma (rHGG), each evaluating different methods of Toca 511 administration (intratumoral injection, injection into the cavity wall following resection, and intravenous injection followed by resection and injection into the cavity wall). Repeated courses of oral Toca FC follow Toca 511 administration. Results to date include good tolerability; no persistent viremia; successful gene transduction within resected tumors: no evidence for clonality by vector insertion site analysis; and increased median overall survival compared to historical controls with all three methods of vector administration. Partial responses and complete responses with a median duration of initial response of > 26months start approximately 6–19months after Toca 511 administration, and are associated with a long term survival. Based on 18Nov2016 data, patients in the resection trial with Toca 5 enrollment criteria and dosing had a clinical benefit rate of 42 % (3CRs, 2PRs, 5 SDs of 24 patients). Examination of IDH1 mutation status shows patients with a response are either wildtype or mutant. Preliminary data from these studies supported initiation of a randomized, Phase 2/3 study in patients with rHGG (NCT02414165) in 2015. Updated pooled safety data, immune response findings, and efficacy data for the Phase 1 studies will be presented.
Published: 2017

7. MEDICAL RADIATION THERAPIES

Author: I. Ahmed, A. Biswas, S. Krishnamurthy, P. Julka, G. Rath, M. Back, D. Huang, C. Gzell, J. Chen, M. Kastelan, P. Gaur, H. Wheeler, S. N. Badiyan, C. G. Robinson, J. R. Simpson, D. D. Tran, K. M. Rich, J. L. Dowling, M. R. Chicoine, E. C. Leuthardt, A. H. Kim, J. Huang, S. R. Michaelsen, I. J. Christensen, K. Grunnet, M.-T. Stockhausen, H. Broholm, M. Kosteljanetz, H. S. Poulsen, M. Tieu, E. Lovblom, M. Macnamara, W. Mason, D. Rodin, E. Tai, K. Ubhi, N. Laperriere, B.-A. Millar, C. Menard, B. Perkins, C. Chung, J. Clarke, A. Molinaro, J. Phillips, N. Butowski, S. Chang, A. Perry, J. Costello, A. DeSilva, J. Rabbitt, M. Prados, A. L. Cohen, C. Anker, D. Shrieve, B. Hall, K. Salzman, R. Jensen, H. Colman, O. Farber, U. Weinberg, Y. Palti, B. Fisher, H. Chen, D. Macdonald, G. Lesser, S. Coons, D. Brachman, S. Ryu, M. Werner-Wasik, J.-P. Bahary, A. Chakravarti, M. Mehta, T. Gupta, V. Nair, S. Epari, J. Godasastri, A. Moiyadi, P. Shetty, S. Juvekar, R. Jalali, U. Herrlinger, N. Schafer, J. Steinbach, A. Weyerbrock, P. Hau, R. Goldbrunner, R. Kohnen, H. Urbach, W. Stummer, M. Glas, C. Houillier, H. Ghesquieres, C. Chabrot, C. Soussain, G. Ahle, S. Choquet, P. Faurie, J.-O. Bay, J. Vargaftig, C. Gaultier, E. Nicolas-Virelizier, K. Hoang-Xuan, O. Iskanderani, F. Izar, A. Benouaich-Amiel, T. Filleron, E. Moyal, C. Iweha, S. Jain, E. Melian, A. Sethi, K. Albain, D. Shafer, B. Emami, X.-T. Kong, S. Green, E. Filka, R. Green, W. Yong, P. Nghiemphu, T. Cloughesy, A. Lai, S. Mallick, S. Roy, S. Purkait, S. Gupta, P. K. Julka, G. K. Rath, C. Marosi, J. Thaler, C. Ay, A. Kaider, E.-M. Reitter, J. Haselbock, M. Preusser, B. Flechl, C. Zielinski, I. Pabinger, S.-I. Miyatake, M. Furuse, T. Miyata, E. Yoritsune, S. Kawabata, T. Kuroiwa, Y. Muragaki, T. Maruyama, H. Iseki, J. Akimoto, S. Ikuta, M. Nitta, K. Maebayashi, T. Saito, Y. Okada, S. Kaneko, A. Matsumura, K. Karasawa, Y. Nakazato, T. Kayama, L. B. Nabors, K. L. Fink, T. Mikkelsen, D. Grujicic, R. Tarnawski, D.-H. Nam, M. Mazurkiewicz, M. Salacz, L. Ashby, L. Thurzo, V. Zagonel, R. Depenni, J. R. Perry, J. Henslee-Downey, M. Picard, D. A. Reardon, N. Nambudiri, L. Nayak, D. LaFrankie, P. Wen, D. Ney, J. Carlson, D. Damek, P. Blatchford, L. Gaspar, B. Kavanagh, A. Waziri, K. Lillehei, K. Reddy, C. Chen, I. Rashed, K. Barton, D. Anderson, V. Prabhu, R. Rusch, M. Belongia, M. Maheshwari, S. Firat, D. Schiff, A. Desjardins, M. Glantz, M. Chamberlain, W. Shapiro, S. Gopal, K. Judy, S. Patel, A. Mahapatra, J. Shan, D. Gupta, K. Shih, J. A. Bacha, D. Brown, W. J. Garner, A. Steino, R. Schwart, S. Kanekal, M. Li, L. Lopez, H. A. Burris, C. Soderberg-Naucler, A. Rahbar, G. Stragliotto, A. J. Song, A. M. S. Kumar, E. S. Murphy, T. Tekautz, J. H. Suh, V. Recinos, S. T. Chao, J. Spoor, K. Korami, J. Kloezeman, R. Balvers, C. Dirven, M. Lamfers, S. Leenstra, A. Sumrall, D. Haggstrom, A. Crimaldi, J. Symanowski, P. Giglio, A. Asher, S. Burri, G. Sunkersett, Z. Khatib, C. M. Prajapati, E. E. Magalona, M. Mariano, I. M. Sih, R. Torcuator, W. Taal, H. Oosterkamp, A. Walenkamp, L. Beerenpoot, M. Hanse, J. Buter, A. Honkoop, D. Boerman, F. de Vos, R. Jansen, F. van der Berkmortel, D. Brandsma, R. Enting, J. Kros, J. Bromberg, I. van Heuvel, M. Smits, R. van der Holt, R. Vernhout, M. van den Bent, W. Wick, C. Suarez, J. Rodon, P. Forsyth, I. Gueorguieva, A. Cleverly, T. Burkholder, D. Desaiah, M. Lahn, L. Zach, D. Guez, D. Last, D. Daniels, O. Nissim, Y. Grober, C. Hoffmann, D. Nass, A. Talianski, R. Spiegelmann, Z. Cohen, and Y. Mardor
Subjects: Abstracts, Cancer Research, medicine.medical_specialty, Text mining, Oncology, business.industry, Medicine, Medical physics, Neurology (clinical), business, Medical radiation
Published: 2013
Full Text: View/download PDF

8. CLIN-ONGOING CLINICAL TRIALS

Author: Albert Lai, James E. Herndon, Charles G. Eberhart, Sarah Milla, Erina Yoritsune, Paula L. Griner, Jaishri O. Blakeley, Masayuki Kanamori, Charles J. Nock, Alva B. Weir, Antonio Omuro, Teiji Tominaga, Leigh Ann Bailey, Nancy Contreras, Sam Ryu, Wolfgang Wick, Kelly Wallen, Xingde Li, Lauren E. Abrey, David H. Harter, Gene H. Barnett, Glenn Stevens, Allan H. Friedman, Gabriele E. Tsung, D.M. Brown, Michael A. Vogelbaum, Ameer Abutaleb, Stefan M. Pfister, Emese Filka, T. Cloughesy, Tulika Ranjan, Andrew B. Lassman, Michael D. Prados, Serena Desideri, Timothy F. Cloughesy, Stuart A. Grossman, Eric C. Holland, Darell D. Bigner, Ryo Nishikawa, Sajeel Chowdhary, Boro Dropulic, Lisa M. DeAngelis, Shinji Kawabata, Frank Saran, Thomas J. Kaley, Warren P. Mason, Elizabeth Hovey, Shaan M. Raza, Patricia Lefferts, Amber E Kerstetter, Roger Henriksson, Cathy Brewer, William J. Garner, Lisa Rogers, Lawrence Kleinberg, Heather J. McCrea, Wenxuan Liang, Mario E. Lacouture, Elliot McVeigh, Toshihiko Kuroiwa, John Simes, Craig Nolan, Mark Rosenthal, Jeffrey H. Wisoff, Paul Rosenblatt, Hillard M. Lazarus, James J. Vredenburgh, Andrew E. Sloan, Hua Fung, Igor T. Gavrilovic, Anna K. Nowak, Olivier Chinot, Richard Schwartz, Helen Wheeler, Stacey Green, Tom Mikkelsen, David Zagzag, Michael C. Bloom, Geneviève Legault, Shin-Ichi Miyatake, Ann Livingstone, Elena Pentsova, Henry S. Friedman, Erin Hartnett, Xiaobu Ye, Katherine B. Peters, Jeffrey C. Allen, Dona Kane, Gregg Shepard, Abhay Sanan, Toshihiro Kumabe, Alfredo Quinones-Hinojosa, Tomo Miyata, Amanda Merkelson, Michael Badruddoja, Kathryn M. Field, Jessica Mavadia, Jill S. Barnholtz-Sloan, Jane S. Reese, Matthias A. Karajannis, Hugo Guerrero-Cazares, Stanton L. Gerson, Mythili Shastry, Jeremy N. Rich, Yukihiko Sonoda, Emmy Ludwig, John Sampson, Christopher L. Brown, John H. Suh, Baldassarre Stea, Heather Embree, Kate Sawkins, John D. Hainsworth, Carmen Kut, Vincent L. Giranda, Phioanh L. Nghiemphu, David T.W. Jones, Howard A. Burris, Cabaret Trial Investigators, Girish Dhall, Lawrence Cher, John A. Boockvar, Ingo K. Mellinghoff, Annick Desjardins, David M. Peereboom, Ryuta Saito, Motomasa Furuse, Jeffrey G. Supko, Yoji Yamashita, Kartik Kesavabhotla, Kent C. Shih, Andrey Korshunov, Samuel T. Chao, Marjorie Pazzi, Jeffrey A. Bacha, Bhardwaj Desai, Kurt Schroeder, Robert H. Miller, Lloyd M. Alderson, Jiefeng Xi, Rajul Shah, Naoko Takebe, Richard M. Green, Alireza Mohammad Mohammadi, Kenneth J. Cohen, Michael Fisher, Naomi E. Rance, and Magalie Hilton
Subjects: Clinical trial, Abstracts, Cancer Research, medicine.medical_specialty, Oncology, business.industry, medicine, Neurology (clinical), Intensive care medicine, business
Published: 2012
Full Text: View/download PDF

9. METABOLIC PATHWAYS

Author: J. W. Locasale, T. Melman, S. S. Song, X. Yang, K. D. Swanson, L. C. Cantley, J. M. Asara, E. T. Wong, S. Adams, N. Braidy, C. Teo, G. Guillemin, M. Philippe, C. Carole, T. David, G. Eric, N.-M. Isabelle, M. de Paula Andre, B. Marylin, C. Olivier, O. L'Houcine, F.-B. Dominique, P. Leukel, C. Seliger, A. Vollmann, B. Jachnik, U. Bogdahn, P. Hau, X. Liu, V. S. Kumar, C. M. McPherson, L. Chow, A. Kendler, B. Dasgupta, S. Piya, E. White, S. Klein, H. Jiang, F. Lang, W. K. Alfred Yung, C. Gomez-Manzano, J. Fueyo, A. Vartanian, A. Guha, K. E. Fenton, M. Abdelwahab, A. C. Scheck, D. Guo, F. Reinitz, M. Youssef, C. Hong, D. Nathanson, D. Akhavan, D. Kuga, A. N. Amzajerdi, H. Soto, S. Zhu, I. Babic, A. Iwanami, K. Tanaka, B. Gini, J. DeJesus, D. D. Lisiero, T. Huang, R. Prins, P. Wen, H. I. Robbins, M. Prados, L. DeAngelis, I. Mellinghoff, M. Mehta, C. D. James, A. Chakravarti, T. Cloughesy, P. Tontonoz, P. Mischel, J. Phillips, J. Mukherjee, C. Cowdrey, J. Wiencke, R. O. Pieper, R. Bachoo, I. Marin-Valencia, S. Cho, D. Rakheja, K. Hatanpaa, T. Mashimo, V. Vemireddy, P. Kapur, L. Good, X. Sun, J. Pascual, M. Takahashi, O. Togao, J. Raisanen, E. A. Maher, R. DeBerardinis, C. Malloy, C. Choi, D. Mathews, C. Madden, B. Mickey, S. Zheng, S. Ronen, I. Park, L. E. Jalbert, M. Ito, T. Ozawa, J. J. Phillips, D. B. Vigneron, S. M. Ronen, and S. J. Nelson
Subjects: Abstracts, Cancer Research, Oncology, Neurology (clinical)
Published: 2011
Full Text: View/download PDF

10. Brain tumor treatment: Chemotherapy and other new developments

Author: C GRAHAM and T CLOUGHESY
Subjects: Oncology (nursing)
Published: 2004
Full Text: View/download PDF

11. Nivolumab (nivo) in combination with radiotherapy (RT) ± temozolomide (TMZ): Updated safety results from CheckMate 143 in pts with methylated or unmethylated newly diagnosed glioblastoma (GBM)

Author: Gordana Vlahovic, N. Butowski, John Sampson, Solmaz Sahebjam, Michael Carleton, Alba A. Brandes, Michael Lim, T. Cloughesy, Prashni Paliwal, David A. Reardon, Antonio Omuro, Joachim M. Baehring, Ricardo Zwirtes, and Von Potter
Subjects: 0301 basic medicine, Brachial Plexus Neuritis, Oncology, medicine.medical_specialty, Temozolomide, business.industry, medicine.medical_treatment, Checkmate, Hematology, Newly diagnosed, medicine.disease, Radiation therapy, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, business, Glioblastoma, medicine.drug
Published: 2017
Full Text: View/download PDF

12. OS07.3 Nivolumab in Combination With Radiotherapy With or Without Temozolomide in Patients With Newly Diagnosed Glioblastoma: Updated Results From CheckMate 143

Author: T. Cloughesy, Gordana Vlahovic, N. Butowski, John Sampson, Joachim M. Baehring, David A. Reardon, Antonio Omuro, Ricardo Zwirtes, Solmaz Sahebjam, and Michael Lim
Subjects: Oncology, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Checkmate, ORAL PRESENTATIONS, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, 0502 economics and business, medicine, Survival rate, Temozolomide, business.industry, 05 social sciences, O-6-methylguanine-DNA methyltransferase, Cancer, medicine.disease, Radiation therapy, 030220 oncology & carcinogenesis, 050211 marketing, Neurology (clinical), Nivolumab, business, medicine.drug, Glioblastoma
Abstract: Background: Patients with glioblastoma (GBM) have a 5-year survival rate of approximately 5%, indicating that novel therapeutic options are critically needed. Nivolumab, a fully human IgG4 monoclonal antibody inhibitor of the programmed death-1 receptor, has provided durable and clinically significant responses in multiple cancer types. In CheckMate 143 (NCT02017717), exploratory cohorts 1c and 1d evaluated the safety and tolerability of nivolumab in combination with radiotherapy (RT) ± temozolomide (TMZ) in patients with newly diagnosed GBM. Methods: In cohort 1c, patients with methylated, unmethylated, or indeterminate MGMT were treated with nivolumab 3 mg/kg every 2 weeks (Q2W) in combination with standard RT and concurrent TMZ (75 mg/m2 daily), followed by adjuvant TMZ (150–200 mg/m2 for 5 days per 28-day cycle for ≥ 6 cycles). I n cohort 1d, patients with unmethylated MGMT received nivolumab 3 mg/kg Q2W with standard RT without TMZ. Patients in both cohorts continued to receive nivolumab 3 mg/kg Q2W until confirmed disease progression or unacceptable toxicity. Results: Enrollment in the study has been completed (N = 110 patients); 57 patients with methylated (19%), unmethylated (68%), or indeterminate (12%) MGMT were treated in cohort 1c and 53 patients with unmethylated (96%) or indeterminate (4%) MGMT were treated in cohort 1d. Treatment discontinuations in cohorts 1c (39%) and 1d (51%) resulted from suspected radiographic progression (1c, 19%; 1d, 43%), patient decision (1c, 9%), study drug toxicity (1c, 5%; 1d, 4%), death (2% each), adverse event (AE) unrelated to study drug (1c, 2%), or unknown cause (2% each). Treatment-related AEs (TRAEs) occurred in 67% (1c) and 70% (1d) of patients, with the most common (≥ 15% in either cohort [1c, 1d]) being fatigue (28%, 26%), headache (21%, 13%), and increased ALT (16%, 9%). Grade 3–4 TRAEs reported in > 2 patients in either cohort (1c, 1d) included increased ALT (5%; 6%) and lipase (2%; 8%). AEs leading to discontinuation in cohort 1c were increased transaminases (5%) and asthenia, fatigue, and hypotension (2% each); in cohort 1d, AEs leading to discontinuation included increased ALT, increased lipase, herpes simplex virus encephalitis, and acute injury (2% each). No treatment-related deaths were reported. Signals of enhanced immune cell infiltration were observed in some patients who had surgery on study for suspected disease progression. Updated efficacy results will be presented. Conclusions: In this first prospective clinical trial of an immune checkpoint inhibitor in patients with newly diagnosed GBM, data suggest that nivolumab combined with RT ± TMZ was well tolerated, with no new safety signals. Rapid accrual in this study supports the feasibility of conducting a trial in patients with newly diagnosed unmethylated MGMT GBM without TMZ. Encouraging results warrant phase 2/3 studies, which have been initiated.
Published: 2017
Full Text: View/download PDF

13. NEURO/MEDICAL ONCOLOGY

Author: Irene Helenowski, Naoya Hashimoto, Jan J. Heimans, Toshiki Yoshimine, Johan A F Koekkoek, Evelyne Emery, José L. Asencio, Andrea Chamczuck, Carly Bridge, Gilbert Faure, Barbara-Ann Millar, Arthur Rosiello, Michela Casanova, John Freymann, Giulio Bertani, Jun-ich Adachi, Christian LaFougere, Julianne Bloom, Paul Vincent Opinaldo, Tobey J. McDonald, Alexander Khandji, Maciej M. Mrugala, Agnieszka Kowalska, Clifford G. Robinson, Josef Pichler, Jayesh Mehta, Lisa M. DeAngelis, Katie Slusarz, Rachel Grossman, Juan Armando Mejía, Sadhana Kannan, In Ah Kim, Pierre Soubeyran, Nabil Ahmed, Matthew J. Matasar, David A. Reardon, Marie-Laure Tanguy, Andrea Pace, Vani Santosh, Tackeun Kim, Adrienne C. Lahti, John E. Donahue, Pavlina Poloskova, Marc H. A. Jansen, Nilanjana Banerji, Margaret Schwartz, Matthias Kirsch, Robert Jeraj, Guus A.M.S. van Dongen, Samuel Singer, Tom J. Snijders, Santosh Kesari, Riccardo Soffetti, Takashi Sasayama, Diana Ly, Kaoru Kurisu, Carsten Friedrich, Shinji Kawabata, Cedric Revil, Michael A. Jacobs, Ryuichi Hirayama, Wan-Soo Yoon, Kathleen Lupica, Christopher Reilly, Takuichiro Hideo, Miguel Gil, Josep Garcia, Ming Zheng, Edward K. Avila, Mairéad G McNamara, Hartmut Uschmann, Jeffrey S. Weinberg, Craig H. Moskowitz, Jörg Hense, Manmeet Ahluwalia, Georg Bjarnason, David Corwin, Shakti Ramkissoon, Jad Alshami, Eric C. Leuthardt, Paul Dilfer, Margaret Patton, Lindsey Heathcock, Cees van Montfort, Rakesh Kumar Gupta, Akihiko Yoshida, Carmine Maria Carapella, Guy K. Mckhann, Marian Hajduch, Meinhard Nevinny-Stickel, Patricia Bruns, Ashish Suri, Hernán Carranza, David A. Gutman, Carlos Yepes, Patrick Y. Wen, T. Cloughesy, Anna Kaltenboeck, Carlos Bartels, Paul D. Brown, Lisa Fichtel, Lorenzo Giammattei, Steven Hamilton, Nobuyuki Takayama, Nan Lin, Jan Drappatz, Roland Eils, Akihiro Tsuboi, Patrick Urban, Minesh P. Mehta, Remy Gressin, Zarnie Lwin, Clarence Eng, Ian F. Dunn, Sin-Soo Jeun, Alva B. Weir, Elisa Trevisan, silviya Meletath, Fumiyuki Yamasaki, Scott N. Hwang, Navya Nambudiri, Timothy F. Cloughesy, Paolo Rampini, Kathryn J. Ruddy, Justin Kirby, Marc C. Huisman, Normand Laperriere, Abajo Guijarro, Alberto González-Aguilar, David M. Peereboom, Antoine F. Carpentier, Steven M. Greenberg, Chikashi Ishioka, Sarah C. Gaffey, Sneha Arya, Guy M. McKhann, Richard Curry, Takashi Watanabe, Keishi Makino, Radek Trojanec, Hideo Takeshima, Joseph F. Megyesi, Jasmina I. Ivanova, Victor Rodriguez Berrocal, Marcel Kool, Eric Burton, Sandra K. Johnston, Hideyuki Arita, Konstantina Karabatsou, Robert C. Rostomily, Sean Grimm, Ralph G. Dacey, Karl Olson, Sonia Gómez, Harry C. Schouten, Christof M. Kramm, Fred H. Hochberg, Darren Hargrave, Kazuhiko Sugiyama, Wilhelm Boogerd, Stefano Tiziani, Christine McCluskey, Albert H. Kim, Tejpal Gupta, Ida Martinelli, Friedrich-Wilhelm Kreth, Lennea Coombs, Keith L. Ligon, J. Manuel Sarmiento, David R. Macdonald, Holly Dickinson, Cristian Massacesi, Basile Wittwer, Jung-Il Lee, Volker Hovestadt, Mark Smolkin, Sampath Somanna, Ingo K. Mellinghoff, Nancy Ann Oberheim Bush, Sanjeev Francis, Roland Goldbrunner, Jai Ho Choi, John Sampson, Roy Allan Dominique Torcuator, Kathleen R. Lamborn, Simon V. Liubinas, Daniel J. Sargent, Christina K. Cramer, Francine Armentano, Heather Leeper, Stefan Rutkowski, Prakash Shetty, Arivazhagan Arimappamagan, Alicia Ortega, Enrique Jiménez, Kazuhiro Tanaka, Kolette D. Fly, Seunggu Han, Nicolas U. Gerber, David Schiff, Antonella Castellano, Isabel Arrillaga-Romany, Robert J. Wechsler-Reya, Sophie Taillibert, Macarena de la Fuente, Wolfgang Wick, Monica Bennett, Francesco Cognetti, John de Groot, Michael Gonzales, Leon D. Ortiz, Yoshiaki Shiokawa, George Sachs, Ivo Tremont, Charles A. Conrad, Michael D. Taylor, Igor J. Barani, Shannon Langmead, Lisa Sturla, Doosik Kong, Rebecca D. Folkerth, Garrett Riggs, Yoon-La Choi, Carole Soussain, Calvin Soh, Peter Canoll, Mariza Daras, Melissa Hoag, James Rigas, Dana Cernea, Liu Diane, Kenji Wakiya, Sandra Silberman, Ivan A. Reveles, Jeffrey S. Wefel, Wenting Wu, Marie Blonski, MA Majaid, Vanessa A. Nestor, Maurits W.C.B. Sanders, Cynthia Harrison, Ruxandra Costa, Andrea Hawkins-Daarud, Mark R. Gilbert, Ruth Katz, Masayuki Kanamori, Tomek Janicki, Aaron C. Spalding, Dong-Sup Chung, Lauren Foresman, Fateme Salehi, Allan H. Friedman, Eric P. Winer, Robert Kwiecien, Joachim Kuehl, Motoo Nagane, Stanislaw Burzynski, Tomokazu Aoki, Gregory N. Fuller, Nina Paleologos, Darell D. Bigner, Max Wintermark, Adam E. Flanders, Eiichi Ishikawa, Subramanian Hariharan, Doreen Pachow, Glen Stevens, Ulrich Schüller, Jennifer Lycette, Jennifer Garst, Jeffery T. Williams, Gordana Vlahovic, Tjeerd J. Postma, Tribhwan Vats, Isabel Arrilaga, Krista Follmer, Henry S. Friedman, Kenneth Schwartz, James Perry, Jonas M. Sheehan, Christian Grommes, Annette M. Molinaro, Seung-Ho Yang, Peter Lichter, Naoki Kagawa, Trish Whitcomb, Monica Loghin, Amanda L. Bergner, Miroslav Vaverka, Jayashree Kalpathy-Cramer, Chitra Sarkar, Thomas Davidson, Nithya Ramnath, Leland Rogers, Roberta Rudà, Steven A. Toms, Martin Gore, Khê Hoang-Xuan, Emmanuel Gyan, Hani Malone, Jun-ichi Adachi, Jennifer Rifenburg, Stefan M. Pfister, Luis Carlos Mayor, Vanja Vaccaro, Hannah E. Goldstein, Karen Fink, Eva Dombi, Timothy Cloughsey, Sabina Eigenbrod, Jiri Ehrmann, Li Li, Pamela R. Jackson, Makoto Ohno, Craig Nolan, Gerald P. Linette, Tatjana Seute, Eric Bouffet, Patricia M. M. B. Soetekouw, David J. Pisapia, Marc Remke, Susan Snodgras, David Tran, Keiichi Kobayashi, Warren P. Mason, Setsu Sakamoto, Chiara Bosa, Gabriele Schackert, Alfred Yung, David Cachia, Toshihiko Kuroiwa, María Ángeles Vaz Salgado, F. Lonnqvist, Francesca Piludu, Alvina Acquaye, Keisuke Ueki, Jung Ho Han, Kathy Newell, Mythili Shastry, Yoon Jae Cho, Marco Riva, Laura M. Fayad, Kristin Diefes, André O. von Bueren, Ina Ly, Beatrix Lutiger, Hiroyoshi Suzuki, Jeanette K. Doorduijn, Eiji Kohmura, Olivier Chinot, Ichiyo Shibahara, Nathalie Jansen, Marta Del Álamo de Pedro, Scott L. Pomeroy, Andreas Zwergal, Terri S. Armstrong, Elmar Kirches, Daniel P. Cahill, Howard A. Fine, Cezary Szczylik, Stéphane Oudard, Gregg C. Shepard, Mark G. Kris, Andrea Milbourne, Dominique Jennings, Marco Locatelli, Dereck Amakye, Takumi Kudo, Simon Bailey, Alessandra Fabi, Taketoshi Maehara, Soumen Khatua, Caroline Houllier, Klaus J. Müller, Jaishri O. Blakeley, Karen Kelly, Jonathon Yun, Thomas Gergel, Diane Liu, Eric T. Wong, Alin Borha, Brian J. Williams, Rakesh Jalali, Birgit Geoerger, Naosuke Nonoguchi, Julie Walker, Jasmin Jo, Manmohan Singh, Mary Noel, Denise Lally-Goss, Tracy T. Batchelor, Andrea Falini, Maximilian Niyazi, Jeffrey Raizer, Martin J. van den Bent, Aleksandra Gruslova, Phioanh L. Nghiemphu, Kristin R. Swanson, Maaike J. Vos, Jethro Hu, Rebeca Alcalce Pampliega, Craig S. Sauter, Leena Ketonen, Michael A. Vogelbaum, Donald Picker, Robert Hawkins, Chris Halpin, Otto S. Hoekstra, Elizabeth Vera-Bolanos, Ahmad Awada, Sawan Kumar, Alexandra Benouaich-Amiel, Joseph Pernicone, Noriyuki Kawabata, Andrew H. Kaye, David Brachman, Kurt A. Jaeckle, Cameron J. Nowell, Maria Carlo, Tom Mikkelsen, Jorg Dietrich, Tomonari Suzuki, Kohei Fukuoka, Philippe Aftimos, Christine Schmid-Tannwald, Vera Wenter, Valeria Conte, Scott Turner, Brian J A Gill, John D. Cullen, Jiayi Huang, Saurabh Dahiya, Vincent Delwail, Lien Bekaert, Priya Kumthekar, Roberta Seidman, Scott R. Plotkin, Priya Deshpande, Christopher Zalewski, Vaibhav Patel, Peter Kurniali, Martha Nowosielski, Zvi Ram, Susan M. Chang, Dannis G. van Vuurden, Stuart A. Grossman, Vaishali Suri, Rajan Jain, Christine Carico, Ying Yuan, Yoji Yamashita, Bojana Milojkovic-Kerklaan, Yannick Kerloeguen, Michael B. Sisti, Rameen Beroukhim, Andrea Artoni, Frances McSherry, John J. Evans, Mark E. Shaffrey, Lauren E. Abrey, Akshal S. Patel, Laura Bernal-Vaca, Rolf-Dieter Kortmann, Robert Grubb, Mimi Lee, Jörg-Christian Tonn, Shinobu Yamada, Andrés Quintero, Kazuhiko Mishima, Ania Marszalek, Stephen Gancher, Amal Melhem-Bertrandt, Takamitsu Fujimaki, Monika Warmuth-Metz, George Avgeropoulos, Rifaquat Rahman, Franck Bourdeaut, Frank Feleppa, Jennifer Clarke, Meredith A. Reid, Maria Werner-Wasik, Andrew D. Norden, Kenneth D. Swanson, Jeffrey N. Bruce, Chae-Yong Kim, Steven S. Rosenfeld, Haiyan Jiang, Oliver Schnell, Toshihiro Kumabe, Michael J. Sullivan, W. Gladdines, Glenn J. Lesser, Chang-Ho Yun, Epari Sridhar, Sophie Lebouvier-Sadot, Andrea Baldwin, Chirag G. Patil, Thomas Smith, Shin-Ichi Miyatake, Renato LaRocca, Kent C. Shih, Russell C. Rockne, Katsu Mizukawa, Antonio Omuro, Ryuta Saito, Mohamed H. Hamza, Eunju Hurh, Silke Soucek, Michel Lacroix, Brian J. Scott, Thomas Kaley, Tetsuya Yamamoto, Gregory J. Zipfel, Andrew Lin, Elena Pentsova, Carlos Emilio Restrepo, Utkarsh Bhagat, Masao Matsutani, Andrew B. Lassman, Stephanie L. Pugh, Yasuji Miyakita, Manabu Kinoshita, Christian Hagel, D. Brandsma, Jorge M. Otero, Marco Timmer, Ke Zhang, S. Altintas, Thierry Lamy, Hirofumi Hirano, Mehar Chand Sharma, Wafik S. El-Deiry, Peter A. Sims, Evanthia Galanis, Yong-Kil Hong, Terence J. O'Brien, Haruo Sugiyama, Dieta Brandsma, Loretta Barron, Joshua J. Jacobs, Roger Henriksson, Albert Lai, David White, Xiao-Tang Kong, John D. Hainsworth, Petronella J Lugtenburg, Paul A. Northcott, Maryline Barrie, Kenneth J. Cohen, Tanuj Saaraswat, Xiaobu Ye, Sandra Ruland, Diana M. Haninger, Surasak Phuphanich, Marc C. Chamberlain, Kenneth Aldape, Ewa Matczak, Phyo Kim, Peter Bartenstein, Lumir Hrabalek, Howard Y. Chang, Donatella Tampieri, Fumi Higuchi, Katherine S. Panageas, Allicia C. Girvan, Majid Khan, Stevie Threatt, Tareq Juratli, Mitchel S. Berger, Linda Dirven, Michele Nikolai, Emmanuelle DiTomaso, Sarah Leary, Jan H.M. Schellens, Chuanlu Jiang, Michael Glantz, Harald Sontheimer, Michael D. Prados, Mauricio Lema, Marie-Christine Guiot, Shesh N. Rai, Minhee Won, Carlos Vargas, Eva Galanis, Kazunori Arita, David I. Sandberg, Gianluca Ardolino, Sylvain Choquet, Ondrej Kalita, Michael Rytting, Lorenzo Bello, Luis Ley Urzaiz, Martin J.B. Taphoorn, Kourosh Jafari-Khouzani, Alfred Rademaker, Juan Martinez San Millan, Isabelle Aerts, Sergio Bracarda, John Norton, Mark D. Anderson, Barbara Zarino, Jun Ichi Kuratsu, Nicholas Butowski, Derek R. Johnson, James E. Herndon, Diana Giannarelli, Debra LaFrankie, Filippo Cogiamanian, Yasuyoshi Chiba, Hideo Nakamura, Agnes Jager, Caroline Chung, Paula Warren, Frans S. S. Leijten, Peter Hau, Yusuke Oji, Yuichi Hirose, Kathryn Gilliland, Sadao Kaneko, W. K. Alfred Yung, Roger Stupp, Amy Chung, Yutaka Hata, Mary Frances McAleer, Hee-Won Jung, Miloslava Zlevorová, Brendan Killory, Raymond Sawaya, Anita Chawla, John Trusheim, H. Ian Robins, Judy Lima, Prakash Ambady, Barbara O'Brien, Sonia Bermúdez, Howard Colman, Matthias Gromeier, Jean-Sébastien Guillamo, Maria C. Pietanza, Antonello Vidiri, Laura Guyman, Kristin Swanson, Paul Rosenblatt, Joshua L. Dowling, Lakshmi Nayak, Ashlee Drawz, Yu Jung Kim, Mikael L. Rinne, Shlomit Yust-Katz, Jessi Stevens, Katharine J. Drummond, Patricia Wing, Sarah Taylor, Joshua E. Allen, Ron Schaafsma, John DeGroot, Shigetoshi Yano, Paula Rauschkolb, Anupam Kumar, Soichiro Shibui, M. E. van Linde, Shirish M. Gadgeel, Yoshitaka Narita, Nicholas G. Avgeropoulos, Luca Bertero, Hongjun Wang, Jason K. Rockhill, Suriya Jeyapalan, Yukihiko Sonoda, Hikaru Sasaki, Shirley L. Markant, Masamitsu Nishihara, Daniel J. Brat, Alexandra Flowers, Monica Sierra del Rio, Morgan Prust, Adam M. Sonabend, Pierre A. Robe, James J. Dignam, Julia C. Chisholm, Gregory J. Riely, Mary Gerard, Sajeel Chowdhary, Natalie Jäger, Giovanna M. D'Abaco, James J. Culhane, Tatsunori Okamura, Erik P. Sulman, L. Adriana Esparza, Ivo W. Tremont-Lukats, Emily Porensky, Yoshihiro Oka, Marcelo De Carvalho, Brigitte C. Widemann, Stacey Kalambakas, Rolf D. Kortmann, Stewart Goldman, Jaap C. Reijneveld, Andrew Brenner, Jacob Mandel, Riccardo Draghi, Yunus Arik, Shinji Yamashita, Torsten Pietsch, Tanweer Zaidi, Dawid Schellingerhout, Marta Penas-Prado, Veronica Villani, Adriana Olar, Vanessa L. Merker, Matthias Holdhoff, Joke W. Baars, Katrina H. Smith, Arnab Chakravarti, Giorgio Carrabba, Gertjan J.L. Kaspers, Susan Boulton, Peter A. Forsyth, David T.W. Jones, Anne Baldock, Meier Hsu, Soham Dasgupta, Jeremy Rudnick, Arun Rai, Jessica Sun, Naoki Shinojima, Christian Mawrin, Eita Uchida, Jaswinder Jutla, Koichi Ichimura, Alona Muzikansky, Jean Philippe Maire, Louis B. Nabors, Yuko Matsushita, Emilie Le Rhun, Annick Desjardins, Magali Lecavalier-Barsoum, Laurie Rice, Bradford A. Moffat, Kelly Hempfling, Andrew A. Kanner, Mark W. Kieran, Stephanie M. Robert, Hervé Ghesquières, Alba A. Brandes, E. Sander Connolly, Jingxia Liu, David T. Dicker, Katherine B. Peters, Gregory S. Burzynski, Charles Sweeley, Deborah T. Blumenthal, Nicolás Useche, Tulika Ranjan, Thierry Muanza, Mercedes Garcia Villanueva, Fernando Hakim, Yana Krutoshinskaya, Shintaro Fukushima, Ryo Nishikawa, Damien C. Weber, Michael R. Chicoine, Motomasa Furuse, André Busson, Joseph R. Simpson, Gabriele Röhn, Susanne Koeppen, Arjun Sahgal, Fabio M. Iwamoto, Leland Graves, Sarah Iglseder, Taro Yanagawa, Michael Lahn, Ramaswamy Govindan, Eduardo Roberts Cervantes, Eric S. Wong, Nadine Kliese, Feng Tai, Katja von Hoff, Vincenzo Anelli, Trevor J. Pugh, Andrés F. Cardona, Gebra Cuyun Carter, Yuko Watanabe, Bogdana Suchorska, Manuela Caroli, José Luis Asencio, Eudocia Q. Lee, John Floyd, Lucas Moreno, Samantha J Mills, Jun-ichiro Kuroda, Susan Chi, David N. Louis, Aanchal Kakkar, Elizabeth R. Gerstner, Annika Schlamann, Robert Cavaliere, John L. Villano, Asha Das, Petr Kavan, Takaaki Yanagisawa, Luc Taillandier, Jonathan Fratkin, Günther Stockhammer, Tomasz Janicki, Sherese Fralin, Wafik Zaky, Lisa Scarpace, Kazunari Yoshida, Magalie Hilton, Andrey Korshunov, Aliasgar Moiyadi, Alexandra Gorelick, Alfredo Carrato Mena, Yuya Nishiyama, Riccardo Soffietti, Marina Donativi, Andrew S. Chi, Lauren Schaff, Andrew P. Morokoff, Sophie E. M. Veldhuijzen van Zanten, Hans-Joachim Reimers, John G. Stewart, Clare Ferrigno, Jackson Hamilton, Do-Hyun Nam, Samantha Hammond, Regina Krel, Mika Watanabe, Anna K. Nowak, Elina Tsyvkin, Michael W. McDermott, Jacoline E C Bromberg, Teiji Tominaga, Laila M. Poisson, Lisa Doherty, Alessia Lodi, Vino Apok, Magdalena Kneblova, Michelle Bell, Carl Jaffe, Sunita Dahr, Maria Koh, Pedro Garciarena, J. Gregory Cairncross, Ana Gómez Rueda, Augustus Perez, Ho Jun Seol, Frank Saran, Camillo Porta, Grace Elzinga, Michael Cloney, and Charles P. Hart
Subjects: Cancer Research, medicine.medical_specialty, business.industry, 010403 inorganic & nuclear chemistry, 01 natural sciences, 0104 chemical sciences, 03 medical and health sciences, Abstracts, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, medicine, Medical physics, Neurology (clinical), business
Published: 2013

14. CLIN-NEURO/MEDICAL ONCOLOGY

Author: F. Girardi, C. Braun, Dennis C. Shrieve, Wei Chen, D. Kita, M. F. Fanelli, David Schiff, Sunyoung Ahn, Elizabeth Vera-Bolanos, J. Carrasquillo, S. Singer, James G. Herman, C. Bosa, Julia Selfridge, V. Tohidi, B.-A. Millar, M. Benavides, M. I. D. L. Fuente, Phioanh L. Nghiemphu, Kristin R. Swanson, John P. Kirkpatrick, Jonathan P.S. Knisely, Jörg C. Tonn, Kenneth Aldape, J. C. Streeter, R. Ruda, Seung Hong Choi, R. Curry, J. Yu, Ryo Nishikawa, E. Garoufalis, A. H. Friedman, Kurt A. Jaeckle, W. Zhang, Maryam Fouladi, Y. Odia, Arthur P. Chou, S. Sahebjam, E. Pentsova, Luis Souhami, Y. Yuan, F. N. Santos, C. Mesia, H. Friedman, Jennifer Linn, J. E. Adair, Yong Hwy Kim, Athanasios P. Kyritsis, Zvi Ram, M. G. Muhonen, Tracy T. Batchelor, Alissa A. Thomas, Stuart A. Grossman, M. Nasseri, Pedro Pérez Segura, S. Lacey, S. D. Bell, Helen A. Shih, E. Bit-Ivan, Timothy A. Chan, H. Pentsova, H. Wilson, Fumiko Shimizu, M. Forbes, L. Randolph, S. Kim, Amit Bhatt, Sabina Eigenbrod, T. Seigal, P. Dall'Occa, F. McSherry, R. M. Green, Michael D. Prados, Camilo E. Fadul, A. Guevarra, J.-Y. Han, Guido Reifenberger, E. Franceschi, D. Sageser, Jennie Taylor, Kevin Petrecca, M. K. Nicholas, Teresa Ribalta, Morris D. Groves, J.-Y. Blay, B. C. Beard, C. F. La, A. A. da Costa, K. Murillo-Medina, W. Pfisterer, R. Chu, Nan Lin, M. Ermani, A. J. Neuwelt, Samuel T. Chao, T. Ranjan, W. Taki, Hendrik Janssen, R. Agati, A. Mahta, T. N. Kreisl, E. Perez, J. Fuster, B. D. Fu, David M. Peereboom, N. Gresa-Arribas, Georg Widhalm, M. D'Apuzzo, J. Steinbach, Tom Mikkelsen, Michael Platten, R. Poggi, Sandra Ictech, I. Craven, A. Raghunathan, John B. Fiveash, N. L. Jansen, Rupert Egensperger, B. Badie, S. Medrano, Chul-Kee Park, K. Wong, Tae Min Kim, M. Bartolotti, M. Alejandro, T. Rosser, H.-P. Kiem, Marie-Christine Guiot, S. Gonzalez, J. Ljubimova, T. Furuta, J. Herndon, J. Finlay, Vivian Tabar, M. Hadjivassiliou, Christine Marosi, D. Hammoud, K. Black, S. K. Anderson, F. Bach, Gregory N. Fuller, N. Kased, S. Shpigel, Gianluca Marucci, Michael A. Vogelbaum, S. Bluml, J. Joo, M. D. Groves, X. Ye, Adam L. Cohen, J. A. Butman, M. D. Prados, X. Perez-Martin, R. Sharma, G. Colon-Otero, Richard M. Green, Paul D. Brown, Cornelia Sax, Robert J. Weil, J. Connelly, S. Burri, M. R. Welch, Marc K. Rosenblum, Minesh P. Mehta, Shlomit Yust-Katz, J. Canellas, Ulrich Bogdahn, S. Liker, P. U. Kumthekar, F. Gilles, M. Brock, Aaron T. Wild, A. Guerrero-Maldonado, Janet M. Bruner, A. Balmanoukian, E. Kitzweger, B. Schuknecht, Ayman I. Omar, J. Sampson, R. F. Del Maestro, W. Hruby, Niklas Thon, S. Zhao, F. Aboul-Enein, L. M. Alderson, J. McClain, J. Rudnick, J. Dorr, Vinay K. Puduvalli, Sonia Partap, Y. Hayashi, A. Kessinger, N. A. Shonka, T. Minamoto, D. Z. Lee, L. G. Berriel, T. Xie, J. Shih, J. S. Bubalo, Oscar Lin, J. E. Herndon, Michael Glantz, A. Gupta, H. Sabit, H. Heinrichs, Hans A. Kretzschmar, A. Asher, T. M. Bhavsar, A. Coan, V. A. Levin, M. Landeros, A. K. Choucair, D. Garbossa, G. Stockhammer, Jian Campian, C. J. Vecht, C. Ausch, Linda M. Liau, H. I. Farhat, M. Richards, H. I. Robins, R. Chaudhary, Agnieszka Korfel, Marta Penas-Prado, A. Jensen, I. Lolli, Amar J. Gajjar, K. Papsdorf, L. DeAngelis, Kathryn Beal, L. Phishniak, J. Joyce, Arnab Chakravarti, J. J. Vredenburgh, C. Dealis, A. F. Campos-Gines, Peter Hau, J.-I. Hamada, R. A. Gilbert, T. J. Kaley, Eric T. Wong, Ian F. Pollack, T. Gajewski, A. C. Levy, L. R. Bressler, X. Chen, C. Bernadette, O. Etxaniz, N. Antony, Birgit Flechl, D. Levacic, Byung Se Choi, J. I. Stenner, F. Pinto, Sandra K. Johnston, M. M. Mrugala, David Roberge, M. Wang, P. J. Anderson, H. A. Fine, M. J. Glantz, Alfred Yung, L. Alderson, M. Chamberlain, R. Naor, Jaume Capellades, Se-Hoon Lee, D. G. Brackman, Nathalie Jansen, T. Synold, Terri S. Armstrong, J. Pichler, X.-T. Kong, T. Cloughesy, P. Frankel, R. Valdez-Vazquez, Mathias Kunz, J. Dalmau, A. Baldock, Stewart Goldman, K. Rizzo, M. Nakada, Christoph Meisner, Ryan Merrell, C. Bomprezzi, Tomokazu Aoki, M. R. Gilbert, Jason K. Rockhill, Benjamin Ellezam, C. Sebastian, O. Arrieta, N. Wu, M. Magistrello, T. Patel, Adelheid Wöhrer, M. Sabel, F. Bokstein, V. Gomez-Molinar, S. Yovino, A. Kheder, Gaspar Reynes, R. Packer, M. Ronellenfitsch, Sasan Karimi, David Piccioni, J. M. Stachnik, C. Sebesta, Ryan Shanley, L. T. Chinen, H.-S. Gwak, E. A. Woyshner, D. Reuter, S. Bekker, K. Hunter, B. Haghighi, G. Poepperl, M. C. Chamberlain, W. Massey, M. A. Hamza, R. Cavaliere, Sichen Li, Daniela A. Bota, S. Spiegl-Kreinecker, G. Tatzreiter, Sigmund Hsu, M. Westphal, T. Pietsch, P. D. Barnes, C. Arango, G. Cervantes-Sanchez, C. Grommes, W. Brick, Vera Graute, M. P. Gabay, L. Bertero, Friedrich W. Kreth, F. M. Iwamoto, D. T. Blumenthal, M. Matsutani, K. B. Peters, S. F. Shakur, E. Flanagan, H. T. Kim, M. Simon, Michael Ackerl, Nadia N. Laack, J. Portnow, R. Ruckser, T. F. Cloughesy, H. Wayne Slone, A. A. Erazo-Valle-Solis, Karin Dieckmann, J. Baerhing, R. Soffietti, N. Laperriere, M. J. Gil, R. Fisher, Thierry Muanza, Reema R. Mody, W. Kim, L. Droms, Fabio M. Iwamoto, J. Grimm, Robert B. Jenkins, M. R. Aizenberg, E. Lipp, M. J. Taphoorn, V. Garcia-Navarro, J. H. Suh, Peter Bartenstein, E. Bourekas, Brett Theeler, W. G. Watkin, R. M. Tyson, Mira Zurayk, D. Alexandru, N. Uchiyam, J. Gilreath, A. J. Ramiro, R. Rockne, R. Naruse, M. Krieger, A. Kloet, Petr Kavan, E. Jaffe, D. A. Reardon, Jochen Herms, A. Willson, H. Zwinkels, M. Faedi, A. Moreno-Aspitia, J. Vredenburgh, Herbert H. Engelhard, C. Bridge, Paul W. Sperduto, H. Yoo, P. Friedman, N. Letarte, Tetsuya Ueba, Lisa M. DeAngelis, C. Nolan, Michael Weller, H. Colman, Jürgen Lutz, H. Ian Robins, J. McGregor, Pankaj Jalan, Joseph Landolfi, M. Di Battista, Bogdana Suchorska, Manuela Caroli, G. Nikkhah, A. Leibetseder, K. Aboody, V. Liu, Albert Lai, Yoshiki Arakawa, Kazuhiko Nozaki, G. Dhall, Kenneth R. Hess, Oscar Gallego, A. Naomi, A. Pace, T. M. Nguyen, K. Kawakami, K. DeBraganca, A. A. Brandes, V. K. Puduvalli, Lakshmi Nayak, Charles A. Conrad, Laurie E. Gaspar, P. J. Flynn, S. Ruiz-Gonzalez, Carmen Balana, J. Lange, T. Kaley, Vijay Pandav, J. Herrada, Eugenia Verger, S. Honigschnabel, M. Chen, C. A. Bridge, Yu Jung Kim, Mary Jo T. Necesito-Reyes, Bettina Hentschel, Victor A. Levin, J. Hu, K. Hoang-Xuan, Chae-Yong Kim, W. Sherman, L. Armbruster, T. Yun, C. Carapella, E. L. Diamond, A. Mahapatra, Warren P. Mason, X. Luo, R. C. Rockne, S. G. Crasto, L. Bailey, K. Sanghee, Matthias Preusser, R. Mathew, Jaclyn Wu, D. White, Susumu Miyamoto, A. Omuro, A. Desjardins, P.H. Gutin, J. S. Lee, Andrew D. Trister, Maxwell Lewis Neal, W. Zaky, A. L. Sumrall, C. M. Sperduto, A. L. Baldock, S. Phuphanich, J. Sul, S. H. Shin, E. A. Neuwelt, Heinrich Elinzano, C. Huang, H. S. Friedman, Laura Guyman, Sean Grimm, C. Sanchez, H. Newton, G. Oberhauser, Chunyue Yin, Wolfgang Wick, Caterina Giannini, Veronica Chiang, C. LaFougere, P. Metellus, A. Krauthammer, M. Kinoshita, J. Sheehan, Miguel J. Gil, E. Trevisan, J. Raizer, Shin-Ichi Miyatake, A. Olch, Jin Wook Kim, John L. Villano, Patricia Sneed, Brian P. O'Neill, A. Sahgal, Il Han Kim, A. Brickhouse, K. Herath, C. Zoccoli, M. J. van den Bent, T. Tsukahara, M. Heaney, B. Hassanzadeh, J. Quan, David R. Macdonald, Percy Ivy, D. Liue, John H. Suh, K. Miyashita, T. J. Fraum, W. A. Yung, I. Melguizo-Gavilanes, Maciej M. Mrugala, Matthew J. Matasar, and P. Garciarena
Subjects: Cancer Research, medicine.medical_specialty, Abstracts, Oncology, business.industry, medicine, Medical physics, Neurology (clinical), business
Published: 2012

15. LAB-RADIOBIOLOGY

Author: S. R. Floyd, M. E. Pacold, S. M. Clarke, E. Blake, A. Fydrych, R. Ho, M. J. Lee, D. E. Root, A. E. Carpenter, D. M. Sabatini, C. A. French, J. E. Bradner, C. C. Chen, M. B. Yaffe, E. Le Rhun, F. Massin, A. Lefevre, J. Bonneterre, M. d. C. Bittencourt, G. Faure, R. Hiramatsu, S. Kawabata, Y. Yamada, S.-I. Miyatake, T. Kuroiwa, S. Li, A. P. Chou, W. Chen, R. Chen, Y. Deng, H. S. Phillips, K. F. Faull, T. Cloughesy, L. M. Liau, A. Lai, K. Mori, R. Ishikura, Y. Tomogane, S. Izumoto, N. Arita, J. Piao, G. Auyeung, E. Policarpio, V. Tabar, T. P. C. Yeung, L. Morrison, L. Hoffman, T.-Y. Lee, G. Bauman, S. Yartsev, S. Ryu, A. Kolozsvary, M. Lapanowski, K. Jenrow, S. Brown, J. H. Kim, R. J. Brown, J. Love, D. Warburton, W. McBride, S. Bluml, X. Ren, B. Vanderwaal, J. Jaboin, A. L. Baldock, S. Anh, R. Rockne, M. Neal, K. Clark-Swanson, G. Sterin, A. D. Trister, H. Malone, V. Ebiana, A. M. Sonabend, M. Mrugala, J. K. Rockhill, D. L. Silbergeld, G. M. McKhann, J. N. Bruce, R. Rostomily, P. Canoll, K. R. Swanson, A. Hawkins-Daarud, A. Baldock, C. Bridge, D. Corwin, M. M. Mrugala, K. Yagle, D. Born, and P. Swanson
Subjects: Cancer Research, Abstracts, Oncology, Neurology (clinical)
Published: 2012

16. MEDICAL AND NEURO-ONCOLOGY

Author: G. K. Prithviraj, S. R. Sommers, R. L. Jump, B. Halmos, L. B. Chambless, S. L. Parker, L. Hassam-Malani, M. J. McGirt, R. C. Thompson, K. Hunter, M. C. Chamberlain, E. M. Le, E. L. T. Lee, Z. S. Sadighi, M. L. Pearlman, J. M. Slopis, T. S. Vats, S. Khatua, N. C. DeVito, M. Yu, R. Chen, E. Pan, T. Cloughesy, J. Raizer, J. Drappatz, M. Gerena-Lewis, J. Rogerio, S. Yacoub, A. Desjardin, M. D. Groves, J. DeGroot, M. Loghin, C. A. Conrad, K. Hess, J. Ni, S. Ictech, W. A. Yung, A. B. Porter, A. C. Dueck, N. J. Karlin, J. Olson, J. Silber, A. S. Reiner, K. S. Panageas, F. M. Iwamoto, T. F. Cloughesy, K. D. Aldape, A. L. Rivera, A. F. Eichler, D. N. Louis, N. A. Paleologos, B. J. Fisher, L. S. Ashby, J. G. Cairncross, G. B. Roldan, P. Y. Wen, K. L. Ligon, D. Shiff, H. I. Robins, B. G. Rocque, W. P. Mason, S. A. Weaver, R. M. Green, F. G. Kamar, L. E. Abrey, L. M. DeAngelis, S. C. Jhanwar, M. K. Rosenblum, A. B. Lassman, D. Cachia, L. Alderson, R. Moser, T. Smith, S. Yunus, K. Saito, A. Mukasa, Y. Narita, Y. Tabei, N. Shinoura, S. Shibui, N. Saito, B. Flechl, M. Ackerl, C. Sax, K. Dieckmann, R. Crevenna, G. Widhalm, M. Preusser, C. Marosi, C. Ay, D. Dunkler, I. Pabinger, C. Zielinski, M. Belongia, S. Jogal, K.-H. Schlingensiepen, U. Bogdahn, G. Stockhammer, A. K. Mahapatra, N. K. Venkataramana, V. Oliushine, V. Parfenov, I. Poverennova, P. Hau, P. Jachimczak, H. Heinrichs, A. G. Mammoser, N. A. Shonka, J. F. de Groot, I. Shibahara, Y. Sonoda, T. Kumabe, R. Saito, M. Kanamori, Y. Yamashita, M. Watanabe, C. Ishioka, T. Tominaga, A. Silvani, P. Gaviani, E. Lamperti, A. Botturi, F. DiMeco, G. Broggi, L. Fariselli, C. L. Solero, A. Salmaggi, E. A. Woyshner, F. Shu, Y. S. Oh, S. Iganej, G. Singh, S. L. Vemuri, B. J. Theeler, B. Ellezam, M. R. Gilbert, T. Aoki, H. Kobayashi, S. Takano, R. Nishikawa, M. Nagane, Y. Muragaki, K. Sugiyama, J. Kuratsu, M. Matsutani, L. A. Langford, V. K. Puduvalli, D. Shen, Z.-p. Chen, J.-p. Zhang, D. Bedekar, S. Rand, J. Connelly, M. Malkin, E. Paulson, W. Mueller, K. Schmainda, O. Gallego, M. Benavides, P. P. Segura, C. Balana, M. Gil, A. Berrocal, G. Reynes, J. L. Garcia, P. Murata, S. Bague, M. J. Quintana, V. G. Vasishta, K. Kobayashi, M. Tanaka, K. Tsuchiya, Y. Shiokawa, A. A. Bavle, K. Ayyanar, M. P. Prado, K. R. Hess, V. Liu, J. de Groot, M. E. Loghin, H. Colman, V. A. Levin, W. K. Alfred Yung, J. R. Hackney, C. A. Palmer, J. M. Markert, J. Cure, K. O. Riley, H. Fathallah-Shaykh, L. B. Nabors, M. G. Saria, C. Corle, J. Hu, J. Rudnick, S. Phuphanich, M. M. Mrugala, L. K. Lee, B. D. Fu, D. A. Bota, R. Y. Kim, T. Brown, H. Feely, A. Hu, J. W. Lee, B. Carter, S. Kesari, X.-T. Kong, S. Sparagana, E. Belousova, S. Jozwiak, B. Korf, M. Frost, R. Kuperman, M. Kohrman, O. Witt, J. Wu, R. Flamini, A. Jansen, P. Curtalolo, E. Thiele, V. Whittemore, P. De Vries, J. Ford, G. Shah, H. Cauwel, P. Edrich, T. Sahmoud, D. Franz, M. Khasraw, C. Brown, D. M. Ashley, M. A. Rosenthal, X. Jiang, Y. g. Mou, Z. p. Chen, M. Oh, E. kim, J. Chang, T. A. Juratli, M. Kirsch, G. Schackert, D. Krex, M. Wang, R. Stupp, M. Hegi, K. A. Jaeckle, T. S. Armstrong, J. S. Wefel, M. Won, D. T. Blumenthal, A. Mahajan, C. J. Schultz, S. C. Erridge, P. D. Brown, A. Chakravarti, W. J. Curran, M. P. Mehta, K. F. Hofland, S. Hansen, M. Sorensen, H. Schultz, A. Muhic, S. Engelholm, A. Ask, C. Kristiansen, C. Thomsen, H. S. Poulsen, U. N. Lassen, O. Zalatimo, C. Weston, C. Zoccoli, M. Glantz, S. Rahmanuddin, M. S. Shiroishi, S. Y. Cen, J. Jones, T. Chen, P. Pagnini, J. Go, A. Lerner, J. Gomez, M. Law, Z. Ram, E. T. Wong, P. H. Gutin, M. S. Bobola, M. Alnoor, D. L. Silbergeld, R. C. Rostomily, J. R. Silber, N. Martha, S. Jacqueline, G. Thaddaus, P. Daniel, M. Hans, M. Armin, T. Eugen, S. Gunther, M. Hutterer, H.-M. Tseng, C. M. Zoccoli, A. Patel, K. Rizzo, J. M. Sheehan, A. L. Sumrall, J. J. Vredenburgh, A. Desjardins, D. A. Reardon, H. S. Friiedman, K. B. Peters, L. P. Taylor, M. Stewart, N. A. Blondin, J. M. Baehring, T. Foote, N. Laack, J. Call, M. G. Hamilton, S. Walling, M. Eliasziw, J. Easaw, N. V. Shirsat, R. Kundar, A. Gokhale, A. Goel, A. A. Moiyadi, J. Wang, E. Mutlu, A. Oyan, T. Yan, O. Tsinkalovsky, H. K. Jacobsen, K. M. Talasila, L. Sleire, K. Pettersen, H. Miletic, S. Andersen, S. Mitra, I. Weissman, X. Li, K.-H. Kalland, P. O. Enger, J. Sepulveda, C. Belda, R. Sitt, L. Phishniak, F. Bokstein, M. Philippe, C. Carole, M. d. P. Andre, B. Marylin, C. Olivier, O. L'Houcine, F.-B. Dominique, N.-M. Isabelle, F. Frederic, F. Stephane, D. Henry, M. A. Errico, L. J. Kunschner, R. Soffietti, E. Trevisan, R. Ruda, L. Bertero, C. Bosa, M. G. Fabrini, I. Lolli, R. Jalali, P. K. Julka, A. K. Anand, D. Bhavsar, N. Singhal, R. Naik, S. John, B. S. Mathew, I. Thaipisuttikul, J. Graber, M. Shirinian, A. M. Fontebasso, K. Jacob, N. Gerges, A. Montpetit, A. Nantel, S. Albrecht, N. Jabado, K. Shah, K. Di, M. Linskey, N. Thon, S. Eigenbrod, S. Kreth, J. Lutz, J.-C. Tonn, H. Kretzschmar, A. Peraud, F.-W. Kreth, A. D. Muggeri, J. P. Alderuccio, B. D. Diez, P. Jiang, Y. Chao, M. Gallagher, R. Kim, S. Pastorino, V. Fogal, J. D. Rudnick, C. Bresee, A. Rogatko, S. Sakowsky, M. Franco, S. Lim, A. Lopez, L. Yu, K. Ryback, V. Tsang, M. Lill, A. Steinberg, R. Sheth, S. Grimm, I. Helenowski, A. Rademaker, F. P. Nunes, V. Merker, D. Jennings, P. Caruso, A. Muzikansky, A. Stemmer-Rachamimov, S. Plotkin, A. C. Spalding, T. W. Vitaz, D. A. Sun, S. Parsons, M. R. Welch, A. Omuro, K. Beal, D. Correa, T. Chan, L. DeAngelis, I. Gavrilovic, C. Nolan, A. Hormigo, T. Kaley, I. Mellinghoff, C. Grommes, K. Panageas, A. Reiner, R. Barradas, L. Abrey, P. Gutin, S. Y. Lee, B. Slagle-Webb, M. J. Glantz, J. R. Connor, C. A. Schlimper, H. Schlag, G. Stoffels, F. Weber, D. A. Krueger, M. M. Care, K. Holland, K. Agricola, C. Tudor, A. Byars, D. N. Franz, L. Rice, J. Chandler, R. Levy, K. Muro, L. Nayak, A. D. Norden, T. J. Kaley, A. A. Thomas, C. E. Fadul, L. P. Meyer, E. C. Lallana, M. Gilbert, K. Aldape, J. De Groot, C. Conrad, V. Levin, M. Groves, P. Chris, V. Puduvalli, S. Nagpal, A. Feroze, L. Recht, H. G. Rangarajan, M. W. Kieran, R. M. Scott, S. M. Lew, S. Y. Firat, A. D. Segura, S. A. Jogal, P. U. Kumthekar, S. A. Grimm, M. Avram, J. Patel, V. Kaklamani, K. McCarthy, M. Cianfrocca, W. Gradishar, M. Mulcahy, J. Von Roenn, E. Galanis, S. K. Anderson, J. M. Lafky, T. J. Kaufmann, J. H. Uhm, C. Giannini, S. K. Kumar, D. W. Northfelt, P. J. Flynn, J. C. Buckner, A. I. Omar, D. Schiff, A. Delios, A. Jakubowski, I. Melguizo-Gavilanes, W. Qiao, X. Wang, N. Hashemi-Sadraei, H. Bawa, G. Rahmathulla, M. Patel, P. Elson, G. Stevens, D. Peereboom, M. Vogelbaum, R. Weil, G. Barnett, M. S. Ahluwalia, E. C. Alvord, R. C. Rockne, J. K. Rockhill, R. Rostomily, A. Lai, J. Wardlaw, A. M. Spence, K. R. Swanson, G. Zadeh, H. Alahmadi, J. Wilson, F. Gentili, J. J. Beumer, J. Wright, N. Takebe, R. Gaur, M. Werner-Wasik, A. J. Gupta, A. Campos-Gines, K. Le, C. Arango, M. Richards, M. Landeros, H. Juan, J. H. Chang, J. S. Kim, J. H. Cho, C. O. Seo, A. L. Baldock, R. Rockne, P. Canoll, D. Born, K. Yagle, D. Alexandru, D. Bota, M. E. Linskey, S. Nabeel, S. N. Raval, J. Rosenow, M. Bredel, P. Z. New, S. R. Plotkin, J. G. Supko, W. T. Curry, A. S. Chi, E. R. Gerstner, T. T. Batchelor, N. Hashemi, S. T. Chao, R. J. Weil, J. H. Suh, M. A. Vogelbaum, G. H. Stevens, G. H. Barnett, D. Corwin, C. Holdsworth, R. Stewart, K. Swanson, J. J. Graber, A. R. Anderson, S. Jeyapalan, M. Goldman, J. Boxerman, J. Donahue, H. Elinzano, D. Evans, B. O'Connor, M. Y. Puthawala, A. Oyelese, D. Cielo, M. Blitstein, M. Dargush, A. Santaniello, M. Constantinou, T. DiPetrillo, H. Safran, C. Halpin, F. G. Barker, E. A. Maher, S. Ganji, R. DeBerardinis, K. Hatanpaa, D. Rakheja, X.-L. Yang, T. Mashimo, J. Raisanen, C. Madden, B. Mickey, C. Malloy, R. Bachoo, C. Choi, T. Ranjan, N. Yono, S. J. Han, M. Sun, M. S. Berger, M. Aghi, N. Gupta, and A. T. Parsa
Subjects: Cancer Research, medicine.medical_specialty, Abstracts, Oncology, business.industry, Neuro oncology, medicine, Medical physics, Neurology (clinical), business
Published: 2011

17. RADIOLOGY

Author: S. Bluml, A. Panigrahy, M. Laskov, G. Dhall, M. D. Nelson, J. L. Finlay, F. H. Gilles, H. Arita, M. Kinoshita, N. Kagawa, Y. Fujimoto, N. Hashimoto, T. Yoshimine, J. D. Hamilton, J. Wang, V. A. Levin, P. Hou, M. E. Loghin, M. R. Gilbert, N. E. Leeds, J. F. deGroot, V. Puduvalli, E. F. Jackson, W. K. A. Yung, A. J. Kumar, B. M. Ellingson, T. F. Cloughesy, W. B. Pope, T. Zaw, H. Phillips, S. Lalezari, P. L. Nghiemphu, H. Ibrahim, K. Motevalibashinaeini, A. Lai, R. Harris, L. Douw, M. E. Van de Nieuwenhuijzen, J. J. Heimans, J. C. Baayen, C. J. Stam, J. C. Reijneveld, C. Juhasz, S. Mittal, D. Altinok, N. L. Robinette, O. Muzik, P. K. Chakraborty, G. R. Barger, T. M. Zaw, J. Goldin, W. Chen, M. A. Ahlman, P. Giglio, T. J. Kaufmann, S. K. Anderson, K. A. Jaeckle, J. H. Uhm, D. W. Northfelt, P. J. Flynn, J. C. Buckner, E. Galanis, O. Zalatimo, C. Weston, D. Allison, D. Bota, S. Kesari, M. Glantz, J. Sheehan, R. E. Harbaugh, Y. Chiba, A. Tsuboi, J. Hatazawa, H. Sugiyama, T. Nariai, J. Toyohara, Y. Tanaka, M. Inaji, M. Aoyagi, M. Yamamoto, K. Ishiwara, K. Ohno, L. Jalilian, E. Essock-Burns, S. Cha, S. Chang, M. Prados, N. Butowski, S. Nelson, Y. Kawahara, M. Nakada, Y. Hayashi, Y. Kai, N. Uchiyama, J.-i. Kuratsu, J.-i. Hamada, K. Yeom, J. Rosenberg, J. B. Andre, P. G. Fisher, M. S. Edwards, P. D. Barnes, S. Partap, J. M. Lupo, J. C. Crane, S. M. Chang, S. J. Nelson, C. A. Romanowski, N. Hoggard, D. A. Jellinek, S. Clenton, F. McKevitt, S. Wharton, I. Craven, A. Buller, C. Waddle, J. Bigley, I. D. Wilkinson, P. Metherall, L. J. Eckel, G. F. Keating, N. M. Wetjen, C. Giannini, C. Wetmore, R. Jain, J. Narang, A. S. Arbab, L. Schultz, L. Scarpace, T. Mikkelsen, A. Babajni-Feremi, L. Poisson, D. Gutman, C. Jaffe, J. Saltz, A. Flanders, B. Daniel, L. Zach, D. Guez, D. Last, D. Daniels, C. Hoffman, Y. Mardor, N. Guha-Thakurta, J. M. Debnam, C. Kotsarini, D. Jellinek, P. D. Griffiths, N. Khandanpour, P. Bambrough, S. Prabhu, R. L. Bassett, W. A. Yung, C. J. Campen, S. Soman, K. W. Yeom, M. J. Vos, J. Berkhof, T. J. Postma, E. Sanchez, E. M. Sizoo, F. J. Lagerwaard, J. Buter, D. P. Noske, R. R. Colen, B. Mahajan, F. A. Jolesz, P. O. Zinn, A. Molinaro, K. Lawton, D. Alexandru, M. E. Linskey, M. M. Chaumeil, B. Gini, H. Yang, A. Iwanami, S. Subramanian, T. Ozawa, E. J. Read, R. O. Pieper, P. Mischel, C. D. James, S. M. Ronen, P. S. LaViolette, E. Cochran, M. Al-Gizawiy, J. M. Connelly, M. G. Malkin, S. D. Rand, W. M. Mueller, K. M. Schmainda, A. D. Cohen, M. Prah, C. J. Hartman, X. J. Qiao, R. He, M. Brown, and T. Cloughesy
Subjects: Cancer Research, Abstracts, Oncology, Neurology (clinical)
Published: 2011

18. PEDIATRICS CLINICAL RESEARCH

Author: R. Antony, M. Zagardo, M. Gujrati, J. Lin, M. Al-Rahawan, A. Broniscer, R. Bhardwaj, C. Hampton, V. Ozols, M. Chakravadhanula, E. Bouffet, C. Hawkins, K. Scheinemann, S. Zelcer, D. Johnston, L. Lafay-Cousin, V. Larouche, N. Jabado, A. S. Carret, J. Hukin, D. Eisenstat, G. Pond, K. Poskitt, B. Wilson, U. Bartels, U. Tabori, G. Dhall, K. Haley, J. Finlay, T. Rushing, R. Sposto, R. Seeger, J. Garvin, K. Rupani, E. Stark, R. Anderson, N. Feldstein, J. Grill, D. Hargrave, M. Massimino, T. Jaspan, P. Varlet, C. Jones, P. Morgan, M. C. Le Deley, A. Azizi, A. Canete, F. Saran, J. Bachir, L. Bubuteishvili-Pacaud, R. Rousseau, G. Vassal, S. Gupta, N. Robinson, N. Dhir, K. Wong, S. Zhou, T. Kumabe, T. Kawaguchi, R. Saito, M. Kanamori, Y. Yamashita, Y. Sonoda, T. Tominaga, T. Miyagawa, C. Nwachukwu, R. Youland, N. Laack, I. Filipek, M. Drogosiewicz, M. P.- Polnik, E. Swieszkowska, B. Dembowska-Baginska, E. Jurkiewicz, D. Perek, W. Grajkowska, M. Roszkowski, G. Sobol, K. Musiol, J. Wachowiak, B. Kazmierczak, J. P. - Pogorzelski, W. Mlynarski, B. Z.- Szewczyk, M. Wysocki, E. Niedzielska, J. Kowalczyk, H. W. - Slusarz, W. Balwierz, E. Z. - Czepko, A. Szolkiewicz, M. Perek-Polnik, M. Lastowska, M. Chojnacka, M. Tarasinska, S. Perreault, K. Chao, V. Ramaswamy, D. Shih, M. Remke, B. Luu, S. Schubert, P. Fisher, S. Partap, H. Vogel, M. Taylor, L. Goumnerova, Y.-J. Cho, N. Robison, R. Brown, T. Cloughesy, T. B. Davidson, M. Krieger, M. Berger, A. Perry, F. Gilles, J. L. Finlay, J. Khemani, B. Britt, J. Grimm, M. I. Ruge, T. Blau, V. Hafkemeyer, C. Hamisch, K. Klinger, T. Simon, Z. Sadighi, B. Ellezam, M. Guindani, J. Ater, Y. Shimizu, H. Arai, M. Miyajima, K. Shimoji, A. Kondo, E. Shinohara, S. Perkins, T. DeWees, I. Slavc, M. Chocholous, U. Leiss, C. Haberler, A. Peyrl, A. A. Azizi, K. Dieckmann, A. Woehrer, C. Dorfer, T. Czech, T. Spence, D. Picard, M. Barszczyk, S.-K. Kim, Y.-S. Ra, J. Fangusaro, H. Toledano, H. Nakamura, X. Fan, K. M. Muraszko, H.-K. Ng, W. Halliday, M. Shago, C. E. Hawkins, A. Huang, M. Suzuki, S. V. van Zanten, M. Jansen, D. van Vuurden, E. Hulleman, S. Idema, D. Noske, N. Wolf, H. Hendrikse, P. Vandertop, G. J. Kaspers, K. Muller, A. Schlamann, M. Warmuth-Metz, T. Pietsch, S. Pietschmann, R.-D. Kortmann, C. M. Kramm, A. O. von Bueren, S. Walston, T. Williams, D. Hamstra, K. Oh, C. Pelloski, N. Zhukova, J. Pole, M. Mistry, I. Fried, N. Lapperiere, P. Dirks, J. An, N. Alon, P. Nathan, M. Greenberg, and D. Malkin
Subjects: Cancer Research, medicine.medical_specialty, business.industry, 03 medical and health sciences, Abstracts, 0302 clinical medicine, Clinical research, Oncology, 030220 oncology & carcinogenesis, Family medicine, medicine, Neurology (clinical), business, 030217 neurology & neurosurgery
Published: 2011

19. OMICS AND PROGNOSTIC MARKERS

Author: F. Moriera, K. So, P. Gould, D. Kamnasaran, R. L. Jensen, I. Hussain, D. H. Gutmann, D. Gorovets, E. R. Kastenhuber, E. Pentsova, L. Nayak, J. T. Huse, M. J. van den Bent, L. A. Gravendeel, T. Gorlia, J. M. Kros, P. Wesseling, J. Teepen, A. Idbaih, M. Sanson, P. A. S. Smitt, P. J. French, W. Zhang, J. Zhang, K. Hoadley, B. Carter, S. Li, C. Kang, Y. You, C. Jiang, S. Song, T. Jiang, C. Chen, C. Grimm, M. Weiler, R. Claus, D. Weichenhan, C. Hartmann, C. Plass, M. Weller, W. Wick, R. B. Jenkins, H. Sicotte, Y. Xiao, B. L. Fridley, P. A. Decker, M. L. Kosel, T. M. Kollmeyer, S. R. Fink, A. L. Rynearson, T. Rice, L. S. McCoy, I. Smirnov, T. Tehan, H. M. Hansen, J. S. Patoka, M. D. Prados, S. M. Chang, M. S. Berger, D. H. Lachance, J. K. Wiencke, J. L. Wiemels, M. R. Wrensch, M. H. Gephart, E. Lee, S. Kyriazopoulou-Panagiotopoulou, L. Milenkovic, X. Xun, Y. Hou, W. Kui, M. Edwards, S. Batzoglou, W. Jun, M. Scott, J. E. Hobbs, J. Tipton, T. Zhou, N. L. Kelleher, J. P. Chandler, J. Schwarzenberg, J. Czernin, T. Cloughesy, B. Ellingson, C. Geist, M. Phelps, W. Chen, M. Nakada, Y. Hayashi, W. Obuchi, S. Ohtsuki, T. Watanabe, C. Ikeda, K. Misaki, D. Kita, N. Uchiyama, T. Terasaki, J.-i. Hamada, L. Hiddingh, B. Tops, E. Hulleman, G.-J. L. Kaspers, W. P. Vandertop, D. P. Noske, T. Wurdinger, J. W. Jeuken, A. P. See, T. Hwang, D. Shin, J. H. Shin, Y. Gao, M. Lim, M. Hutterer, M. Michael, U. Gerold, S. Karin, G. Ingrid, D. Florian, M. Armin, T. Eugen, G. Eberhard, S. Gunther, R. W. Cook, K. Oelschlager, H. Sevim, L. Chung, H. T. Wheeler, R. C. Baxter, K. L. McDonald, A. Chaturbedi, L. Yu, Y.-H. Zhou, A. Wong, R. Fatuyi, M. E. Linskey, I. Lavon, T. Shahar, D. Zrihan, A. Granit, Z. Ram, T. Siegal, D. J. Brat, L. A. Cooper, D. A. Gutman, C. S. Chisolm, C. Appin, J. Kong, T. Kurc, E. G. Van Meir, J. H. Saltz, C. S. Moreno, H. J. Abuhusain, A. S. Don, R. P. Nagarajan, B. E. Johnson, A. B. Olshen, M. Xie, J. Wang, V. Sundaram, P. Paris, T. Wang, J. F. Costello, A. E. Sijben, S. H. Boots-Sprenger, J. Boogaarts, J. Rijntjes, J. M. Geitenbeek, J. van der Palen, H. J. Bernsen, O. Schnell, S. A. Adam, S. Eigenbrod, H. A. Kretzschmar, J.-C. Tonn, U. Schuller, P. W. Sperduto, N. Kased, D. Roberge, Z. Xu, R. Shanley, X. Luo, P. K. Sneed, S. T. Chao, R. J. Weil, J. Suh, A. Bhatt, A. W. Jensen, P. D. Brown, H. A. Shih, J. Kirkpatrick, L. E. Gaspar, J. B. Fiveash, V. Chiang, J. P. Knisely, C. M. Sperduto, N. Lin, M. P. Mehta, M. M. Kwatra, T. M. Porter, K. E. Brown, J. E. Herndon, D. D. Bigner, R. H. Dahlrot, B. W. Kristensen, S. Hansen, E. P. Sulman, D. P. Cahill, M. Wang, M. Won, M. E. Hegi, K. D. Aldape, M. R. Gilbert, E. S. Sadr, A. Tessier, M. S. Sadr, J. Alshami, C. Sabau, R. Del Maestro, M. L. Neal, R. Rockne, A. D. Trister, K. R. Swanson, S. Maleki, M. Back, M. Buckland, D. Brazier, K. McDonald, R. Cook, N. Parker, H. Wheeler, L. Jalbert, A. Elkhaled, J. J. Phillips, H. A. Yoshihara, R. Parvataneni, R. Srinivasan, G. Bourne, S. Cha, S. J. Nelson, M. Gilbert, D. Cahill, M. Hegi, H. Colman, M. Mehta, E. Sulman, A. Constantin, J. Phillips, H. Yoshihara, S. Nelson, S. Gunn, X. T. Reveles, B. Tirtorahardjo, M. N. Strecker, and L. Fichtel
Subjects: Cancer Research, Abstracts, Text mining, Oncology, business.industry, Medicine, Neurology (clinical), Computational biology, business, Omics
Published: 2011

20. TUMOR MODELS (IN VIVO/IN VITRO)

Author: S. T. Keir, D. A. Reardon, H. S. Friedman, D. D. Bigner, D. Y. Lee, A. Kaul, W. W. Pong, S. M. Gianino, C. R. White, R. J. Emnett, D. H. Gutmann, J. P. Robinson, M. VanBrocklin, A. Jydstrup-McKinney, L. Saxena, S. L. Holmen, R. L. Price, J. Song, K. Bingmer, P. Zimmerman, A. Rivera, M. Oglesbee, J.-Y. Yi, B. Kaur, C. Cook, C.-H. Kwon, E. A. Chiocca, Y. Hu, A. Chaturbedi, J. Nelson, M. E. Linskey, Y.-H. Zhou, R. Sarabia-Estrada, C. A. Molina, I. Jimenez-Estrada, Z. L. Gokaslan, T. F. Witham, J.-P. Wolinsky, A. Bydon, D. M. Sciubba, A. Luchman, O. Stechishin, A. Weljie, M. Blough, J. Kelly, S. Nguyen, R. Hassam, D. Livingstone, O. Cseh, H. D. Hoc, J. G. Cairncross, S. Weiss, M. Monje, S. S. Mitra, M. E. Freret, M. S. Edwards, I. L. Weissman, P. A. Beachy, T. Ozawa, N. A. Charles, J. T. Huse, K. Helmy, M. Squatrito, E. C. Holland, B. C. Kennedy, A. Sonabend, L. Lei, P. Guarnieri, R. Leung, C. Soderquist, J. Yun, J. Bruce, P. Canoll, M. Castelli, B. Kennedy, S. Rosenfeld, R. K. Balvers, J. J. Kloezeman, D. Heijsman, A. Kremer, P. J. French, C. M. Dirven, S. Leenstra, M. L. Lamfers, J. Lazovic, H. Soto, D. Piccioni, A. Chou, S. Li, R. Prins, L. Liau, T. Cloughesy, A. Lai, W. Pope, T. G. Johns, B. Day, A. Wilding, B. Stringer, A. W. Boyd, P. Li, B. Mcellin, M. Maddie, B. Wohlfeld, S. Kernie, R. Kim, E. A. Maher, and R. Bachoo
Subjects: Cancer Research, Abstracts, Oncology, Neurology (clinical)
Published: 2011

21. A modeling-based factor extraction method for determining spatial heterogeneity of Ga-68 EDTA kinetics in brain tumor

Author: Y. Zhou, S.C. Huang, T. Cloughesy, C.K. Hoh, and K. Black
Published: 2002
Full Text: View/download PDF

22. 8707 Clinical assessment of corticosteroid use and neurocognitive function in patients with glioblastoma at first or second relapse treated with bevacizumab in the BRAIN study

Author: T. Cloughesy, J. Zazzali, H.S. Friedman, A. Das, M. Zheng, J.J. Vredenburgh, Jeffrey S. Wefel, M.K. Samant, and L. Fang
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Bevacizumab, business.industry, medicine.disease, Internal medicine, medicine, Physical therapy, In patient, Corticosteroid use, business, Neurocognitive, Glioblastoma, medicine.drug
Published: 2009
Full Text: View/download PDF

23. Phase I study of aflibercept (VEGF Trap) and temozolomide in newly diagnosed, high-grade glioma

Author: Patrick Y. Wen, Lisa M. DeAngelis, Tracy T. Batchelor, Xiaobu Ye, Stuart A. Grossman, Alice P. Chen, J. F. De Groot, J. Drappatz, Mark R. Gilbert, M. Prados, Antonio Omuro, T. Cloughesy, W. K. A. Yung, Susan M. Chang, Frank S. Lieberman, Joy D. Fisher, and K. Lamborn
Subjects: Oncology, Placental growth factor, Cancer Research, medicine.medical_specialty, Temozolomide, business.industry, medicine.medical_treatment, Brain tumor, medicine.disease, Surgery, Radiation therapy, Vascular endothelial growth factor A, Regimen, Concomitant, Internal medicine, Medicine, business, Aflibercept, medicine.drug
Abstract: 2043 Background: Anti-vascular endothelial growth factor (VEGF) therapy has shown promise in the treatment of high-grade gliomas (HGG). Aflibercept is a recombinant human fusion protein that acts as a soluble decoy receptor for VEGFA, VEGF-B and placental growth factor (PlGF), depleting circulating levels of these growth factors. Methods: The Adult Brain Tumor Consortium (ABTC) conducted a phase I trial of aflibercept and temozolomide (TMZ) in patients with newly diagnosed high-grade gliomas (HGG). Three cohorts were examined: Cohort 1: Aflibercept with radiotherapy and concomitant temozolomide; Cohort 2: Aflibercept and adjuvant temozolomide using the 5/28 regimen; and Cohort 3: Aflibercept and adjuvant temozolomide using the 21/28 day regimen. Eligibility criteria included histologically proven newly-diagnosed glioblastoma (GBM) or anaplastic glioma (AG), > 18 yrs old, KPS > 60, adequate bone marrow reserve and organ function. Patients initially received 2 mg/kg of aflibercept every 2 weeks. If no dose-...
Published: 2011
Full Text: View/download PDF

24. Prediction of GBM outcome using combined analysis of MGMT protein expression and promoter methylation

Author: Linda M. Liau, Jose Carrillo, Albert Lai, Anh Tran, Richard M. Green, Wei Chen, T. Cloughesy, S. Lalezari, William H. Yong, He-Jing Wang, Robert Elashoff, Phioanh L. Nghiemphu, A. P. Chou, O. E. Solis, and Paul S. Mischel
Subjects: Cancer Research, Standard of care, Temozolomide, Methyltransferase, business.industry, Postoperative radiotherapy, Bioinformatics, medicine.disease, Protein expression, nervous system diseases, Oncology, Promoter methylation, Cancer research, Medicine, business, medicine.drug, Glioblastoma
Abstract: 2003 Background: The standard of care for patients with newly-diagnosed glioblastoma (GBM) consists of postoperative radiotherapy and temozolomide (TMZ). O6-methylguanine-DNA methyltransferase (MGM...
Published: 2011
Full Text: View/download PDF

25. Phase I study of vorinostat in combination with temozolomide in patients with malignant gliomas

Author: Andrew B. Lassman, John G. Kuhn, M. Prados, Frank S. Lieberman, Serena Desideri, Stuart A. Grossman, Susan M. Chang, W. K. A. Yung, Renee M. McGovern, J. Drappatz, Patrick Y. Wen, K. Lamborn, H. I. Robins, Igor Espinoza-Delgado, Mark R. Gilbert, Vinay K. Puduvalli, Matthew M. Ames, Joel M. Reid, T. Cloughesy, and Xiaobu Ye
Subjects: Cancer Research, Temozolomide, business.industry, medicine.drug_class, Histone deacetylase inhibitor, medicine.disease, nervous system diseases, Phase i study, Oncology, medicine, Cancer research, In patient, business, Vorinostat, medicine.drug, Glioblastoma
Abstract: 2032 Background: Vorinostat (V) is an oral histone deacetylase inhibitor. In preclinical studies it inhibits growth of glioblastoma (GBM) lines and has additive activity when combined with temozolo...
Published: 2011
Full Text: View/download PDF

26. Phase II study of XL184 (BMS 907351), an inhibitor of MET, VEGFR2, and RET, in patients (pts) with progressive glioblastoma (GB)

Author: J. Drappatz, T. Mikkelsen, Marc C. Chamberlain, David Schiff, M. Prados, J. F. De Groot, David A. Reardon, T. Cloughesy, Patrick Y. Wen, and Tracy T. Batchelor
Subjects: Antitumor activity, Cancer Research, biology, business.industry, VEGF receptors, Phases of clinical research, respiratory system, medicine.disease, Oncology, cardiovascular system, biology.protein, Cancer research, Medicine, In patient, business, neoplasms, circulatory and respiratory physiology, Glioblastoma
Abstract: 2006 Background: XL184 is an oral, potent inhibitor of MET, VEGFR2 and RET that has demonstrated clinical antitumor activity. In solid tumors, the MTD was 175 mg qd. Elevated levels of VEGFR2 and M...
Published: 2010
Full Text: View/download PDF

27. A phase I safety and pharmacokinetic study of XL765 (SAR245409), a novel PI3K/TORC1/TORC2 inhibitor, in combination with temozolomide (TMZ) in patients (pts) with newly diagnosed malignant glioma

Author: T. Cloughesy, Antonio Omuro, Patrick Y. Wen, Phioanh L. Nghiemphu, Linh Nguyen, Andrew D. Norden, Ingo K. Mellinghoff, and K. Rajangam
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Temozolomide, business.industry, Newly diagnosed, medicine.disease, Pharmacokinetics, Glioma, Internal medicine, medicine, In patient, business, PI3K/AKT/mTOR pathway, medicine.drug
Abstract: 3085 Background: PI3K pathway dysregulation has been implicated in resistance to TMZ in preclinical glioma models. XL765, a potent and selective inhibitor of class I PI3K isoforms and TORC1 and TOR...
Published: 2010
Full Text: View/download PDF

28. Use of bevacizumab to facilitate up-front chemoradiation in poor-risk patients with glioblastoma multiforme by improving neurologic function

Author: T. Cloughesy, Albert Lai, Richard M. Green, Emily Woyshner, and L. Nghiemphu
Subjects: Cancer Research, medicine.medical_specialty, Poor risk, Bevacizumab, business.industry, medicine.disease, nervous system diseases, Surgery, Neurologic function, Oncology, Edema, medicine, Radiology, medicine.symptom, business, medicine.drug, Glioblastoma
Abstract: 2059 Background: Poor postoperative neurologic function due to mass effect and steroid-refractory perilesional edema often limits the ability of patients with glioblastoma multiforme (GBM) to toler...
Published: 2010
Full Text: View/download PDF

29. Phase I/II study of sorefenib and erlotinib for patients with recurrent glioblastoma (GBM) (NABTC 05–02)

Author: M. Prados, K. Lamborn, John Tim Wright, Frank S. Lieberman, T. Cloughesy, Lauren E. Abrey, H. I. Robins, Mark R. Gilbert, Patrick Y. Wen, and John G. Kuhn
Subjects: Sorafenib, Oncology, Cancer Research, medicine.medical_specialty, Combination therapy, business.industry, Pharmacology, North American Brain Tumor Consortium, Temsirolimus, medicine.anatomical_structure, Targeted Molecular Therapy, Internal medicine, Clinical endpoint, medicine, Bone marrow, business, neoplasms, PI3K/AKT/mTOR pathway, medicine.drug
Abstract: 2005 Background: Single agent targeted therapy has been disappointing in GBM. Combination therapy simultaneously targeting both EGFR and the MAP kinase pathway may be more effective. Methods: The NABTC conducted a phase I/II study of sorafenib (VEGFR/PDGFR/Raf inhibitor) in combination with erlotinib (EGFR inhibitor) in recurrent GBM. Eligibility criteria included histologically proven GBM, radiologic progression, > 18 yrs old, KPS > 60, adequate bone marrow reserve, and organ function. There was no limit on the number of prior therapies for phase I and no more than two prior relapses for phase II. No enzyme-inducing antiepileptic drugs were allowed. Dose-finding used a standard 3 + 3 design and the MTD was defined as the dose with DLTs in 1/6 or fewer patients. The primary endpoint for the phase II component was PFS6 (p0 = 15%; p1 = 35%). A 2-stage design was used. If > 4 of the initial 19 patients achieved PFS6, an additional 14 patients would be accrued for a total of 33 patients. Results: In phase I, 17 patients were enrolled. Median age 50 years (35–69); median prior chemotherapy 1 (1–3). The initial doses were sorafenib 200 mg bid and erlotinib 100mg qd. MTD was 400 mg bid of sorafenib daily combined with 100 mg of erlotinib daily. At this dose 1/6 evaluable patients had a DLT (grade 4 lipase). Other grade 3 or 4 toxicities included transaminitis, hypertension, hypophosphatemia, and increased lipase. Pharmacokinetic studies showed no alterations in sorafenib PK, but no accumulation of erlotinib, suggesting a drug-drug interaction with sorafenib altering erlotinib metabolism or clearance. In phase II, 19 patients were accrued to stage I. Median age 51 years (30–75); median prior chemotherapy 2 (range 1–3). Phase II toxicity and outcome data are not yet mature but will be available at the time of presentation. Conclusions: This combination was moderately well-tolerated. MTD was below other combination phase I studies. Sorafenib affected the PK of erlotinib preventing drug accumulation. Phase II toxicity and outcome data will be reported. [Table: see text]
Published: 2009
Full Text: View/download PDF

30. Phase I/II study of erlotinib and temsirolimus for patients with recurrent malignant gliomas (MG) (NABTC 04–02)

Author: S. M. Chang, J. Kuhn, K. Lamborn, T. Cloughesy, I. Robins, F. Lieberman, A. Yung, J. Dancey, M. Prados, and P. Wen
Subjects: Cancer Research, Oncology
Abstract: 2004 Background: Glioblastomas (GBM) frequently have EGFR amplification/mutations and inactivation of PTEN. Although single agent EGFR and mTOR inhibitors have limited activity, combinations of these agents may be more effective. Methods: The North American Brain Tumor Consortium conducted a phase I/II study of the EGFR inhibitor erlotinib in combination with the mTOR inhibitor temsirolimus in recurrent MG. Eligibility criteria were histologically proven GBM and anaplastic gliomas (AG), radiologic progression, >18 years old, KPS >60, adequate bone marrow and organ function. There was no limit on the number of prior relapses for phase I and no more than two prior relapses for phase II. Patients must not be receiving enzyme-inducing antiepileptic drugs. The dose of erlotinib was 150 mg/d in phase I and titrated up to maximum of 200mg/d in phase II depending on tolerability. Patients initially received temsirolimus 50 mg i.v. once weekly and the dose adjusted based on toxicities. Escalation was performed in groups of three. MTD was defined as the dose with 1/6 or fewer patients with dose-limiting toxicities (DLTs). Primary endpoint for the phase II component was PFS6. Results: In phase I, 22 patients were enrolled (15 GBM; 7 AG). Median age was 54 years (26–74); median KPS 90 (70–100); median prior relapses 1 (0–3). The MTD was determined to be 150 mg of erlotinib daily combined with 15 mg of temsirolimus weekly. DLTs were rash, mucositis, and liver function abnormalities. Pharmacokinetic data were similar to that for single agent erlotinib and temsirolimus; there was no interaction between the two drugs. AUC accumulation ratios between cycle 1 and 2 for erlotinib and OSI-420 were 3.6 and 4.6, respectively. In phase II, there were 56 patients (including 12 phase I patients treated at the MTD): 40 GBM; 16 AG, median age 47 years (20–72); median KPS 90 (range 60–100), median prior relapses 1 (range 1–3). Six patients discontinued therapy as a result of toxicities. For GBM patients, there was no PR, 30% SD, and PFS6 was 12.5%. For AG patients there was 12.5% PR, 12.5% SD, and PFS6 was 6.25%. Conclusions: The combination of erlotinib and temsirolimus was associated with a higher than expected incidence of toxicities and had minimal activity in recurrent MG. [Table: see text]
Published: 2009
Full Text: View/download PDF

31. Phase I/II study of sorafenib and temsirolimus for patients with recurrent glioblastoma (GBM) (NABTC 05–02)

Author: P. Y. Wen, T. Cloughesy, J. Kuhn, K. Lamborn, L. E. Abrey, F. Lieberman, H. I. Robins, J. Wright, M. D. Prados, and M. Gilbert
Subjects: Cancer Research, Oncology
Abstract: 2006 Background: The activity of targeted molecular therapy with single agents has been disappointing in GBM. Combination therapy simultaneously targeting both the PI3k/Akt/mTOR and the MAP kinase pathway may be more effective. Methods: The North American Brain Tumor Consortium conducted a phase I/II study of sorafenib (VEGFR/PDGFR/Raf inhibitor) in combination with temsirolimus (mTOR inhibitor) in recurrent GBM. Eligibility criteria included histologically proven GBM, radiologic progression, > 18 years old, KPS > 60, adequate bone marrow reserve, and organ function. There was no limit on the number of prior relapses for phase I and no more than two prior relapses for phase II. No enzyme-inducing antiepileptic drugs were allowed. Dose-finding used a standard 3 + 3 design with the MTD defined as the dose with DLTs in 1/6 or fewer patients. The primary endpoint for the phase II component was PFS6 (p0 = 15%; p1 = 35%). A 2-stage design was used. If > 4 of the initial 19 patients achieved PFS6, an additional 14 patients would be accrued for a total of 33 patients. Results: In phase I, 13 patients were enrolled. Median age was 50 years (32–59); median prior chemotherapy 1 (1–3). The initial doses were sorafenib 200 mg bid and temsirolimus 25 mg intravenously once weekly. The MTD was 400 mg bid of sorafenib daily combined with 25 mg of temsirolimus weekly. At this dose 1/6 patients had a DLT (grade 3 thrombocytopenia). Other grade 3 or 4 toxicities included transaminitis, hypophosphatemia, fatigue, diarrhea, and hyperlipidemia. Pharmacokinetic data were similar to that for single agent sorafenib and temsirolimus suggesting that there were no significant interaction between the two drugs. In phase II, 19 patients were accrued to stage I. Median age 50 years (24–64); median prior relapses 1 (range 1–2). One patient was found not to have GBM on central review. No patient remained progression free at 6 months, although two patients stopped treatment prior to 26 weeks for other than progression (alternative therapy, cerebral ischemia). As result, the study was terminated and did not proceed to the second stage. Conclusions: The combination of sorafenib and temsirolimus was moderately well-tolerated but did not demonstrate sufficient efficacy in recurrent GBM to warrant further investigation. No significant financial relationships to disclose.
Published: 2009
Full Text: View/download PDF

32. Interaction between sorafenib and erlotinib

Author: Vinay K. Puduvalli, John G. Kuhn, M. Prados, Lisa M. DeAngelis, Frank S. Lieberman, J. Cooper, K. Lamborn, T. Cloughesy, Mark R. Gilbert, and Patrick Y. Wen
Subjects: Sorafenib, Cancer Research, business.industry, Metabolite, PK Parameters, Pharmacology, respiratory tract diseases, chemistry.chemical_compound, Oncology, Pharmacokinetics, chemistry, Maximum tolerated dose, medicine, heterocyclic compounds, Sorafenib 200 MG, In patient, Erlotinib, business, neoplasms, medicine.drug
Abstract: 2500 Background: The combination of sorafenib plus erlotinib was evaluated in patients with recurrent glioblastoma (GBM). In addition to defining the maximum tolerated dose (MTD), pharmacokinetics (PKs) for single agent and combination were determined. Methods: Adults with recurrent GBM with the usual phase I inclusion/exclusion criteria were eligible. No enzyme inducing anti-epileptic agents were allowed. Starting doses for erlotinib and sorafenib were 100mg PO QD and 200 mg PO BID, respectively, for 28 days (a cycle). For cycle 1 PKs, erlotinib was started on day 1 followed on day 2 by sorafenib. Eight plasma samples were collected over 24hrs on days 1, 15 and 28. Sorafenib and its metabolite (N-oxide) were analyzed by HPLC and erlotinib and OSI-420 by LC/MS. PK parameters were characterized by standard non-compartmental methods. Results: The MTD was sorafenib 200 mg PO BID and erlotinib 100 mg PO QD. The PKs for erlotinib (OSI) are displayed below. Conclusions: The PKs for sorafenib are in agreement with previous reports and not affected by the co-administration of erlotinib. However, there is an apparent affect of sorafenib on the PKs of erlotinib. The expected accumulation of erlotinib's Cmax and AUC at steady-state was not observed. This interaction results in at least a 2+ fold decrease in exposure to erlotinib and its active metabolite. The interaction does not appear to be the classical enzyme induction due to the rapidity of the onset/offset. This same phenomenon has been reported with the co-administration of sorafenib with gefitinib (Clin Cancer Res 13:2684,2007). Increasing the maximal velocity (Vmax) of CYP3A4, not the quantity of enzyme, is suggested as a testable hypothesis (J Pharmacol Exp Ther 290:1.1998). The clinical relevance of this interaction with regard to toxicity and efficacy warrants further evaluation. [Table: see text] No significant financial relationships to disclose.
Published: 2009
Full Text: View/download PDF

33. Phase II trials of erlotinib or gefitinib in patients with recurrent meningiomas

Author: Lauren E. Abrey, M. Prados, Patrick Y. Wen, Frank S. Lieberman, T. Cloughesy, Mark R. Gilbert, Jeffrey Raizer, K. Lamborn, Susan M. Chang, and Andrew D. Norden
Subjects: Oncology, Cancer Research, medicine.medical_specialty, biology, business.industry, Gefitinib, Internal medicine, medicine, biology.protein, Effective treatment, In patient, Erlotinib, Epidermal growth factor receptor, business, neoplasms, medicine.drug
Abstract: 2062 Background: No effective treatment is available for recurrent meningiomas when surgical and radiation options are exhausted. The epidermal growth factor receptor (EGFR) is often over-expressed in meningiomas and may promote tumor growth. In open label, single arm phase II studies of the EGFR inhibitors gefitinib (NABTC 00–01) and erlotinib (NABTC 01–03) for recurrent malignant gliomas, we included exploratory subsets of recurrent meningioma patients. We have pooled the data and report the results here. Methods: Patients with recurrent histologically confirmed meningiomas and no more than two previous chemotherapy regimens were treated with gefitinib 500 mg/day or erlotinib 150 mg/day until tumor progression or unacceptable toxicity. Results: Twenty-five eligible patients were enrolled with median age 57 years (range 29–81) and median Karnofsky performance status (KPS) score 90 (range 60–100). Sixteen patients (64%) received gefitinib and nine (36%) erlotinib. Eight patients (32%) had benign tumors, 9 (36%) atypical, and eight (32%) malignant. For benign tumors, the 6-month progression-free survival (PFS6) was 29%, 12-month PFS (PFS12) 0%, 6-month overall survival (OS6) 63%, and 12-month OS (OS12) 50%. For atypical/malignant tumors, PFS6 was 25%, PFS12 19%, OS6 81%, and OS12 68%. There were no significant PFS or OS differences by histology. Of 21 evaluable patients, there were no responses; eight patients (38%) had stable disease, and 13 (62%) had progressive disease. Treatment was well-tolerated. Rash was not a significant predictor of PFS or OS. Conclusions: Neither gefitinib nor erlotinib appear to have significant activity against recurrent meningioma. The role of EGFR inhibitors in meningiomas is unclear but evaluation of EGFR inhibitors in combination with other targeted molecular agents may be warranted. No significant financial relationships to disclose.
Published: 2009
Full Text: View/download PDF

34. A phase II, randomized, non-comparative clinical trial of the effect of bevacizumab (BV) alone or in combination with irinotecan (CPT) on 6-month progression free survival (PFS6) in recurrent, treatment-refractory glioblastoma (GBM)

Author: Lauren E. Abrey, M. Prados, David Schiff, I. Dimery, T. Cloughesy, Z. Maoxia, Patrick Y. Wen, Henry S. Friedman, T. Mikkelsen, and W. K. Yung
Subjects: Oncology, Cancer Research, medicine.medical_specialty, biology, Bevacizumab, Treatment refractory, business.industry, VEGF receptors, medicine.disease, Surgery, Clinical trial, Irinotecan, Internal medicine, medicine, Overall survival, biology.protein, Progression-free survival, business, medicine.drug, Glioblastoma
Abstract: 2010b Background: Effective 2nd-line therapies are absent in GBM leading to poor survival. VEGF upregulation is implicated in GBM tumorigenesis. In a single-arm PhII trial of BV + CPT in recurrent GBM, activity was demonstrated, warranting further investigation of clinical benefit of BV alone, and in combination with CPT (Vredenburgh J, JCO 2007). Methods: From June 2006 to Feb 2007, 167 patients (pts) with recurrent GBM were randomized 1:1 to BV (10 mg/kg q 2 wks) (Arm 1, n=85) or BV + CPT (340 mg/m2 if enzyme-inducing anti- epileptic drugs (AEDs) and 125 mg/m2 for non-AEDs) (Arm 2, n=82), stratified by KPS: 70–80, 90–100, and relapse (1st or 2nd). The co- primary endpoints were PFS6 (defined at 24-weeks) and objective response rate (ORR) determined by an independent radiology facility (IRF), with secondary endpoints of safety, PFS, and duration of response determined by IRF, and overall survival. The trial provided approximately 80% power to detect 13% improvement in PFS6 from an assumed rate of 15%, an...
Published: 2008
Full Text: View/download PDF

35. Phase II single arm trial of aflibercept in patients with recurrent temozolomide-resistant glioblastoma: NABTC 0601

Author: K. Lamborn, M. Prados, T. Cloughesy, W. K. A. Yung, Patrick Y. Wen, Alice P. Chen, Lisa M. DeAngelis, Mark R. Gilbert, J. F. De Groot, Susan M. Chang, and Minesh P. Mehta
Subjects: Placental growth factor, Oncology, Cancer Research, medicine.medical_specialty, Temozolomide, business.industry, Growth factor, medicine.medical_treatment, medicine.disease, Internal medicine, Toxicity, medicine, Clinical endpoint, Progression-free survival, business, medicine.drug, Aflibercept, Glioblastoma
Abstract: 2020 Background: Anti-vascular endothelial growth factor (VEGF) therapy is a promising treatment approach for patients with recurrent glioblastoma. Aflibercept (VEGF Trap) is a recombinantly-produced fusion protein which scavenges both VEGF and placental growth factor (PlGF) removing important ligands for the VEGF family receptors expressed on tumor endothelium. Methods: We report the results of a phase II trial of aflibercept monotherapy for patients with temozolomide-resistant recurrent glioblastoma and anaplastic glioma at first relapse. Patients received 4 mg/kg aflibercept IV every 2 weeks. The primary endpoint was 6-month progression free survival (PFS) and secondary endpoints include radiographic response rate (RR), PFS, overall survival and toxicity. Response was assessed using Macdonald's criteria. At this time, we provide preliminary response and toxicity data but complete information will be available at the time of presentation. Results: A total of 48 patients have been enrolled; 32 patients w...
Published: 2008
Full Text: View/download PDF

36. Phase IIa trial of cilengitide (EMD121974) single-agent therapy in patients (pts) with recurrent glioblastoma (GBM): EMD 121974-009

Author: Martin Picard, Jeffrey Raizer, David Schiff, David A. Reardon, Stefan R. Krueger, T. Cloughesy, Scott R. Plotkin, Karen Fink, B. Nabors, and Tom Mikkelsen
Subjects: Cancer Research, medicine.medical_specialty, biology, business.industry, Recurrent glioblastoma, Integrin, Cilengitide, Pentapeptide repeat, Surgery, chemistry.chemical_compound, Oncology, chemistry, Toxicity, biology.protein, Cancer research, PHASE IIA TRIAL, medicine, Single agent, In patient, business
Abstract: 2002 Background: Our phase IIa study evaluated the safety, toxicity, and clinical activity of the cyclic RGD pentapeptide cilengitide (EMD121974), an inhibitor of integrins avβ3 and avβ5, as a single agent at doses of 500 and 2000 mg in pts with recurrent GBM. Methods: In this multicenter, open-label, randomized, uncontrolled study, pts with GBM and measurable disease that had relapsed after previous temozolomide and radiotherapy were randomized to receive cilengitide at either 500 mg or 2000 mg i.v., 2x/week, until progression. Neurologic exams were performed after every cycle (4 weeks) and MRIs were performed every other cycle. Central, blinded pathology and radiology reviews were performed. The primary endpoint was Progression Free Survival (PFS) at 6 months (6-mth PFS). Secondary endpoints included response, survival, time to disease progression, safety, tolerability and pharmacokinetics (PK). Results: 81 pts accrued (median Karnofsky Performance Status 80%; median age 57 yrs) at 15 sites including 41 at the 500 mg and 40 at the 2000 mg dose levels. Demographic and pretreatment variables were comparable between dose level cohorts. The median number of infusions was 16 [range, 4–179]. PK studies revealed significantly greater exposures among the 2000 mg cohort. Treatment related NCI CTC grade 3 adverse events (AEs) included elevated transaminases (at 500 mg), arthralgia/ myalgia (at 500 mg), and weight increase/ edema (at 2000 mg) in 1 patient, respectively. No grade 4 therapy related AEs were reported. One CTC grade 2 cerebral hemorrhage was reported in a pt at progression. The 6- mth PFS was 16.1% (n=13/81 pts). 10 pts (12.3 %, n=4 with 500 mg, n=6 with 2000 mg) received 12 or more cycles. Six pts (7.4%) remain progression-free and on treatment. Median Overall Survival (mOS) was 6.5 mths [95% CI: 5.2–9.3 mths] in the 500 mg arm and 9.9 mths [95% CI, 6.3–15.7 mths] in the 2000 mg arm. Although not statistically significant, there was a trend towards better tumor control in pts receiving 2000 mg 2x/week. Conclusions: Cilengitide was well tolerated and demonstrated single agent activity in recurrent GBM, with long term disease stabilization in a subset of pts. [Table: see text]
Published: 2007
Full Text: View/download PDF

37. Phase I study of erlotinib and CCI-779 (temsirolimus) for patients with recurrent malignant gliomas (MG) (NABTC 04–02)

Author: T. Cloughesy, M. Prados, K. Lamborn, John G. Kuhn, Patrick Y. Wen, Alison R. Yung, Frank S. Lieberman, Susan M. Chang, Ian Robins, and Janet Dancey
Subjects: Oncology, Cancer Research, medicine.medical_specialty, biology, business.industry, Pharmacology, North American Brain Tumor Consortium, Temsirolimus, medicine.anatomical_structure, Phase i ii, Tolerability, Internal medicine, biology.protein, Medicine, PTEN, Erlotinib, Bone marrow, business, medicine.drug, EGFR inhibitors
Abstract: 2057 Background: Glioblastomas (GBM) frequently have amplification/mutation of EGFR and inactivation of PTEN. Although single agent EGFR and mTOR inhibitors have only modest activity, there is a rationale for combinations of these agents. Methods: The North American Brain Tumor Consortium (NABTC) is conducting a phase I/II study of the EGFR inhibitor erlotinib in combination with the mTOR inhibitor CCI-779 in recurrent MG. Eligibility criteria were histologically proven GBM and anaplastic gliomas (AG), radiologic progression, > 18 yrs old, KPS > 60, adequate bone marrow reserve and organ function. Patients (pts) must not be receiving enzyme inducing antiepileptic drugs. The dose of erlotinib was fixed at 150 mg/d. Patients initially received CCI-779 50 mg intravenously once weekly and the dose was adjusted based on toxicities. Dose-limiting toxicities (DLT), determined during the first 4 weeks of therapy, were defined as any grade (G) 4 hematologic toxicity except for G3 thrombocytopenia, and any G3 or unacceptable G2 non-hematologic toxicities. Escalation was performed in groups of 3. The maximum tolerated dose (MTD) was defined as the dose at which DLTs occurred in no more than 1/6 pts. Results: To date 22 eligible pts have been enrolled (15 GBM; 7 AG). Patient characteristics were 12 male, 10 female; median age: 54 (26–74); median KPS 90 (70–100); median prior chemotherapy regimens 1 (0–3). Two of 3 pts receiving 50 mg of CCI-779 developed DLTs (intolerable G2 rash & mucositis, & G3 liver function abnormalities; G3 rash & dehydration). Three of 6 pts receiving 25 mg of CCI-779 weekly experienced DLTs (G3 rash; G3 rash, diarrhea, dehydration; G3 mucositis & infection). Two of 6 patients receiving weekly 15 mg of CCI-779 experienced G3 rash. The protocol was amended to define a DLT only if > G3 toxicities persisted despite maximal therapy. Six additional pts were treated at 15 mg of CCI-779. One of 6 pts developed a G3 rash. Conclusions: The combination of erlotinib and CCI-779 was associated with a higher than expected incidence of rash and mucositis. The MTD for this combination is likely to be 150 mg/d of erlotinib and 15 mg/d of CCI-779. Final pharmacokinetics and response data will be presented. No significant financial relationships to disclose.
Published: 2007
Full Text: View/download PDF

38. Phase I study of vorinostat (suberoylanilide hydroxamic acid) in combination with temozolomide (TMZ) in patients with malignant gliomas (NABTC 04–03)

Author: Patrick Y. Wen, W. A. Yung, Susan M. Chang, Joel M. Reid, H. I. Robbins, Renee M. McGovern, T. Cloughesy, John G. Kuhn, Matthew M. Ames, M. Prados, and Vinay K. Puduvalli
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Temozolomide, business.industry, medicine.medical_treatment, Pharmacology, North American Brain Tumor Consortium, Phase i study, Radiation therapy, medicine.anatomical_structure, Internal medicine, Suberoylanilide Hydroxamic Acid, medicine, In patient, Bone marrow, business, Vorinostat, medicine.drug
Abstract: 2039 Background: Vorinostat (V) is an oral inhibitor of histone deacetylase. In preclinical studies it inhibits growth of glioblastoma (GBM) cell lines and has supra-additive activity when combined with TMZ. Methods: The North American Brain Tumor Consortium (NABTC) is conducting a phase I study of V in combination with TMZ in patients with malignant gliomas (MG). Eligibility criteria are histologically proven GBM and anaplastic gliomas (AG) who have received radiotherapy and have not progressed on temozolomide, > 18 yrs old, life expectancy > 8 weeks, KPS > 60, adequate bone marrow reserve and organ function. There was no limitation to the type of antiepileptic drugs that could be used. All patients received TMZ at a dose of 150 mg/m2/day on days 1–5 days every 28 days. Variable doses of V were administered with food on days 1–14 every 28 days. Dose-limiting toxicities (DLT), determined during the first 4 weeks of therapy, were defined as any grade 4 hematologic toxicity except for grade 3 thrombocytopenia, and any grade 3 non-hematologic toxicities. Escalation was performed in standard groups of 3. The maximum tolerated dose (MTD) was defined as the dose at which DLTs occurred in no more than 1/6 patients. PKs were determined on cycle 1 for TMZ, V and its metabolites. Results: To date, 19 eligible patients have been enrolled (15 GBM; 4 AG). Patients’ characteristics are 11 male, 8 female; median age 54 yrs (36–78); median KPS 90 (70–100). DLTs were encountered at 300 mg bid of vorinostat (1 grade 3 thrombocytopenia; 1 grade 3 fatigue in 3 patients), 200 mg tid (1 grade 3 nausea, 1 grade 4 thrombocytopenia in 3 patients) and 200 mg twice daily (grade 3 fatigue in 2/6 patients). No DLTs were encountered in 6 patients receiving 300 mg daily. TMZ PKs included [n=16: Cmax 5.2 (± 1.55) μg/ml; AUC 20.1 (±4.66) μg x hr/ml; t1/2 1.9 (±0.32)/hr]. Vorinostat PKs (300mg dose level) were [n=4; Cmax 267 (±174) ng/ml; AUC0–8 603 (±197) ng x hr/ml]. The t1/2 for V and its glucuronide metabolite were identical (1.6 hrs) vs. 5.6 hrs for the acid metabolite. Conclusions: The MTD of vorinostat in combination with TMZ is 300 mg daily on days 1–14 every 28 days. Final PK results, and toxicities from an additional 10 patients enrolled at the MTD will be presented. [Table: see text]
Published: 2007
Full Text: View/download PDF

39. 621 POSTER A phase I study of combination therapy with AEE788, a novel multitargeted inhibitor of ErbB and VEGF receptor family tyrosine kinases, and RAD001, a mTOR inhibitor in recurrent GBM patients

Author: D. Reardon, Charles A. Conrad, William Mietlowski, T. Cloughesy, A. Lai, L. Yung, W. Chen, W. K. A. Yung, C. Cilea, and J. Rich
Subjects: Cancer Research, biology, Combination therapy, business.industry, VEGF receptors, Discovery and development of mTOR inhibitors, Phase i study, Oncology, ErbB, biology.protein, Cancer research, Medicine, AEE788, business, Tyrosine kinase
Published: 2006
Full Text: View/download PDF

40. Combination of temozolomide (TMZ) and irinotecan (CPT-11) showed enhanced activity for recurrent malignant gliomas: A North American Brain Tumor Consortium (NABTC) phase II study

Author: Larry Junck, M. Prados, Susan M. Chang, K. Lamborn, Patrick Y. Wen, T. Cloughesy, W. K. A. Yung, I. Robin, Mark R. Gilbert, and Frank S. Lieberman
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Temozolomide, business.industry, medicine.medical_treatment, Phases of clinical research, Pharmacology, North American Brain Tumor Consortium, medicine.disease, Group A, Group B, Irinotecan, Anticonvulsant, Internal medicine, Glioma, medicine, business, neoplasms, medicine.drug
Abstract: 1521 Background: TMZ, an oral alkylating agent is active in recurrent malignant glioma. CPT-11, a topoisomerase I inhibitor, has also been shown to have modest activity in recurrent malignant glioma. A phase I study by NABTC has demonstrated the safety of combining TMZ and CPT-11 in a q2-week schedule and established the MTD of CPT-11 at 500 mg for patients receiving p450 enzyme inducing anticonvulsant (Group B). This phase II study is to further establish the efficacy of this combination in pts with recurrent malignant glioma. Methods: This is a multicenter phase II trial. All pts had documented recurrent GBM or Anaplastic Gliomas (AA, AO, AOA). TMZ was given at 150 mg/m2/d x 5, q 28d. For pts not receiving p450 enzyme inducing anticonvulsant (Group A), CPT-11 was given at 200 mg/m2, q2-wk, while 500 mg/m2 q2-wk, was given to Group B pts. Results: 51 GBM and 17 AG pts were entered into the study (50 Group A, 18 Group B). Demographic and preliminary outcome data are listed in the table below. Response dat...
Published: 2005
Full Text: View/download PDF

41. A phase I study of AEE788, a novel multitargeted inhibitor of ErbB and VEGF receptor family tyrosine kinases, in recurrent GBM patients

Author: David A. Reardon, William Mietlowski, Margaret Dugan, M. Prados, Paul S. Mischel, T. Cloughesy, Henry S. Friedman, J. Xia, Alfred Yung, and Charles A. Conrad
Subjects: Cancer Research, Dose limiting toxicity, biology, business.industry, VEGF receptors, Pharmacology, Phase i study, Oncology, Pharmacokinetics, ErbB, Maximum tolerated dose, biology.protein, Medicine, AEE788, business, Tyrosine kinase
Abstract: 3063 Background: AEE788 is an oral inhibitor with potent activity against multiple tyrosine kinases, including EGFR, HER2, and VEGFR2. This phase I study was to assess the safety and pharmacokinetics (PK) and to define the maximum tolerated dose (MTD)/dose limiting toxicity (DLT) of AEE788 in GBM patients (pts). Methods: Pts with GBM at 1st or 2nd recurrence were enrolled. Dose escalation followed accelerated titration design: 1 pt/cohort initially with expansion up to 3–6 pts. Two dose escalations occurred simultaneously: pts who received either non-enzyme inducing anticonvulsants (Gp A) or enzyme-inducing anticonvulsants (Gp B). Cardiac assessments were performed. A 24-hr PK was obtained on days 1, 15, and 28. A cycle (cyc) is 28 days. Results: To date, 26 pts (21 1st recurrent, 5 2nd recurrent; 20 male, 6 female), median age 50.5 (range 24–68), were treated with once daily AEE788 at doses of either 50 (2), 100 (6), 200 (1), 400 (3), 450 (1), or 550 (8) mg (Gp A); or 300 (2) or 600 (3) mg (Gp B). Two Gp...
Published: 2005
Full Text: View/download PDF

42. Phase II study of erlotinib in recurrent GBM: Molecular predictors of outcome

Author: M. Prados, D. Eberhard, T. Cloughesy, Scott R. VandenBerg, Paul S. Mischel, Alison R. Yung, Kenneth Aldape, J. Vrendenberg, and B. J. Klencke
Subjects: Cancer Research, integumentary system, biology, business.industry, Phases of clinical research, Orally active, Oncology, Cancer research, biology.protein, medicine, Epidermal growth factor receptor, Erlotinib, business, medicine.drug
Abstract: 1507 Background: Erlotinib (Tarceva) is an orally active, highly potent and selective inhibitor of the epidermal growth factor receptor (EGFR). Preliminary results from this phase II trial of erlot...
Published: 2005
Full Text: View/download PDF

43. Erlotinib HCL for glioblastoma multiforme in first relapse, a phase II trial

Author: A. Yung, J. Vredenburgh, T. Cloughesy, B. J. Klencke, P. S. Mischel, D. D. Bigner, K. Aldape, S. Vanderburg, and M. Prados
Subjects: Cancer Research, Oncology
Published: 2004
Full Text: View/download PDF

44. NABTC phase I/II trial of ZD-1839 for recurrent malignant gliomas and unresectable meningiomas

Author: F. S. Lieberman, T. Cloughesy, H. Fine, J. Kuhn, K. Lamborn, M. Malkin, H. I. Robbins, W. A. Yung, P. Wen, and M. Prados
Subjects: Cancer Research, Oncology
Published: 2004
Full Text: View/download PDF

45. Phase I study of ZD1839 plus temozolomide in patients with malignant glioma. A study of the North American Brain Tumor Consortium

Author: John G. Kuhn, I. A. Robins, W. A. Yung, M. Prados, Patrick Y. Wen, Karen Fink, Susan M. Chang, T. Cloughesy, and Larry Junck
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Temozolomide, business.industry, Prior Chemotherapy Regimens, North American Brain Tumor Consortium, medicine.disease, Group B, Surgery, Phase i study, Internal medicine, Glioma, Cohort, medicine, In patient, business, medicine.drug
Abstract: 1504 Background: To define the MTD of ZD1839 in combination with Temodar in patients with malignant glioma, without (Group A) or with (Group B) enzyme-inducing antiepileptic drugs (EIAEDs). Methods: Eligible pts were > 17 years of age, had KPS ≥60 with stable or progressive malignant glioma, with acceptable laboratory baseline tests. Radiation was completed at least 3-weeks prior to registration. No more than 3 prior chemotherapy regimens allowed. Treatment: Patients started on a continuous dose of ZD1839 (day 1) beginning at 500 mg/day. Temodar started (day 8) at an oral dose of 150 mg/m2/day for 5 days after the ZD1839 and was repeated every 28 days. Temodar could be escalated to 200 mg/m2/day after cycle 1. DLT was defined as any grade 3 or greater non-hematological or any grade 4 hematological toxicity using CTC v 2.0 during the first 35 days of therapy. 3 patients per cohort (Group A or Group B) were enrolled. The dose of ZD 1839 was escalated by 250 mg increments assuming no DLT in each 3-patient gr...
Published: 2004
Full Text: View/download PDF

46. A phase II trial of erlotinib (OSI-774) in patients (pts) with recurrent malignant gliomas (MG) not on EIAEDs

Author: M. Prados, T. Cloughesy, Karen Fink, Patrick Y. Wen, Lauren E. Abrey, Vinay K. Puduvalli, Howard A. Fine, Frank S. Lieberman, I. A. Robins, and Jeffrey Raizer
Subjects: Oncology, Cancer Research, medicine.medical_specialty, biology, business.industry, medicine.drug_class, Histology, medicine.disease, Tyrosine-kinase inhibitor, Internal medicine, medicine, biology.protein, In patient, Erlotinib, Epidermal growth factor receptor, business, Nuclear medicine, medicine.drug, Glioblastoma
Abstract: 1502 Purpose: To evaluate the efficacy of OSI-774, a small molecule tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR), in patients with recurrent malignant gliomas not on enzyme induce anti-convulsant drugs (EIAEDs). Methods: Pts with recurrent MG were treated with OSI-774 at a dose of 150 mg/day continuously. Patients could not have had more than 2 prior chemotherapies. Patients were evaluated for response with MRI every 56 days. PK studies and AGP levels were done in most patients. Results: 67 pts enrolled onto this arm of the study but only the 45 pts with recurrent MG are reported here. Histology: 30 (20M/10F) pts had glioblastoma multiformes (GBMs) and 15 (7M/8F) pts had anaplastic gliomas (AGs). Median age and KPS was 58 years and 80 for GBMs and 43 years and 90 for AGs. The median PFS for GBM was 12 wks (95% CI; 7.6 to 13 weeks) with no GBM pts progression free at 24 weeks; best response was SD in 4 pts. For AGs median PFS was 8.6 wks (CI; 3.7 to 45 wks) with 4 patients still...
Published: 2004
Full Text: View/download PDF

47. Predicting the efficacy of radiotherapy in individual glioblastoma patients in vivo: a mathematical modeling approach.

Author: R Rockne, J K Rockhill, M Mrugala, A M Spence, I Kalet, K Hendrickson, A Lai, T Cloughesy, E C Alvord Jr and, and K R Swanson
Subjects: GLIOBLASTOMA multiforme treatment, CANCER radiotherapy, TREATMENT effectiveness, MATHEMATICAL models in medicine, GLIOMAS, CANCER cell proliferation, CELL migration, PREDICTION models
Abstract: Glioblastoma multiforme (GBM) is the most malignant form of primary brain tumors known as gliomas. They proliferate and invade extensively and yield short life expectancies despite aggressive treatment. Response to treatment is usually measured in terms of the survival of groups of patients treated similarly, but this statistical approach misses the subgroups that may have responded to or may have been injured by treatment. Such statistics offer scant reassurance to individual patients who have suffered through these treatments. Furthermore, current imaging-based treatment response metrics in individual patients ignore patient-specific differences in tumor growth kinetics, which have been shown to vary widely across patients even within the same histological diagnosis and, unfortunately, these metrics have shown only minimal success in predicting patient outcome. We consider nine newly diagnosed GBM patients receiving diagnostic biopsy followed by standard-of-care external beam radiation therapy (XRT). We present and apply a patient-specific, biologically based mathematical model for glioma growth that quantifies response to XRT in individual patients in vivo. The mathematical model uses net rates of proliferation and migration of malignant tumor cells to characterize the tumor''s growth and invasion along with the linear-quadratic model for the response to radiation therapy. Using only routinely available pre-treatment MRIs to inform the patient-specific bio-mathematical model simulations, we find that radiation response in these patients, quantified by both clinical and model-generated measures, could have been predicted prior to treatment with high accuracy. Specifically, we find that the net proliferation rate is correlated with the radiation response parameter (r = 0.89, p = 0.0007), resulting in a predictive relationship that is tested with a leave-one-out cross-validation technique. This relationship predicts the tumor size post-therapy to within inter-observer tumor volume uncertainty. The results of this study suggest that a mathematical model can create a virtual in silico tumor with the same growth kinetics as a particular patient and can not only predict treatment response in individual patients in vivo but also provide a basis for evaluation of response in each patient to any given therapy. [ABSTRACT FROM AUTHOR]
Published: 2010
Full Text: View/download PDF

48. Phase II study of POLY-ICLC in recurrent anaplastic glioma - A North American Brain Tumor Consortium study

Author: Frank S. Lieberman, M. Prados, Larry Junck, Patrick Y. Wen, T. Cloughesy, Susan M. Chang, Ian Robins, Karen Fink, Lisa M. DeAngelis, K. Lamborn, and Alison R. Yung
Subjects: Cancer Research, Pathology, medicine.medical_specialty, business.industry, Phases of clinical research, North American Brain Tumor Consortium, Anaplastic glioma, Oncology, Poly ICLC, medicine, Cancer research, Progression-free survival, business, medicine.drug
Abstract: 1550 Background: The goals of this study were to determine the 6-month progression free survival (PFS) for patients with recurrent anaplastic glioma (AG) treated with the immune-modulatory agent POLY-ICLC, and to evaluate toxicity. Low dose Poly-ICLC has a direct immune enhancing action which includes an increased antibody response to antigen and activation of NK-cells, T-cells, macrophages and cytokines. Previously documented side effects include transient flu-like symptoms, which responds to acetaminophen and pain related to the intramuscular administration. Methods: Eligibility included age >18 years, recurrent AG, no more than 2 prior relapses, normal laboratory parameters and informed consent. Poly-ICLC was administered at 20mcg/kg 3x/week by intramuscular injection in 4 week cycles continuously. Dose reductions were allowed for toxicities. Patients were assessed for tumor response every 2 months. Treatment continued until tumor progression, unacceptable toxicity or patient withdrawal. The study had a 2 stage design with the initial assessment of 6 month PFS for the first 22 patients with possible expansion to a total of 46 patients, if more than 7 patients of the 22 had a 6 month PFS. Results: As of 12/05, 46 patients were treated (49% males). Median age was 42 years (range 21–70 years) and median KPS was 90. The agent was well tolerated and the toxicity profile was as previously reported. The response rate and 6 month PFS of the 22 patients in the first stage of the study was 9% and 23% respectively. Based on these findings the cohort was expanded to 46 patients. Of the 15 patients in the second cohort with at least 1 post treatment response assessment available, there is 1PR and 7 SD (47%). Conclusions: 6 month PFS for the entire cohort continues to be assessed but preliminary results suggest antitumor activity of this agent in recurrent anaplastic glioma. No significant financial relationships to disclose.

49. Reply to comment on: ‘Predicting the efficacy of radiotherapy in individual glioblastoma patients in vivo: a mathematical modeling approach’.

Author: R Rockne, J K Rockhill, M Mrugala, A M Spence, I Kalet, K Hendrickson, A Lai, T Cloughesy, E C Alvord Jr, and K R Swanson
Subjects: RADIOTHERAPY, MATHEMATICAL models, GLIOBLASTOMA multiforme
Abstract: A reply by R. Rockne et al to a letter to the editor about their article "Predicting the Efficacy of Radiotherapy in Individual Glioblastoma Patients in Vivo: A Mathematical Modeling Approach" that was published in a 2010 issue.
Published: 2016
Full Text: View/download PDF

50. ACTION: a randomized phase 3 study of ONC201 (dordaviprone) in patients with newly diagnosed H3 K27M-mutant diffuse glioma.

Author: Arrillaga-Romany I, Lassman A, McGovern SL, Mueller S, Nabors B, van den Bent M, Vogelbaum MA, Allen JE, Melemed AS, Tarapore RS, Wen PY, and Cloughesy T
Subjects: Humans, Double-Blind Method, Adult, Male, Female, Histones genetics, Adolescent, Child, Young Adult, Prognosis, Survival Rate, Quality of Life, Middle Aged, Follow-Up Studies, Aged, Glioma genetics, Glioma drug therapy, Glioma pathology, Brain Neoplasms genetics, Brain Neoplasms drug therapy, Brain Neoplasms pathology, Mutation
Abstract: Background: H3 K27M-mutant diffuse glioma primarily affects children and young adults, is associated with a poor prognosis, and no effective systemic therapy is currently available. ONC201 (dordaviprone) has previously demonstrated efficacy in patients with recurrent disease. This phase 3 trial evaluates ONC201 in patients with newly diagnosed H3 K27M-mutant glioma., Methods: ACTION (NCT05580562) is a randomized, double-blind, placebo-controlled, parallel-group, international phase 3 study of ONC201 in newly diagnosed H3 K27M-mutant diffuse glioma. Patients who have completed standard frontline radiotherapy are randomized 1:1:1 to receive placebo, once-weekly dordaviprone, or twice-weekly dordaviprone on 2 consecutive days. Primary efficacy endpoints are overall survival (OS) and progression-free survival (PFS); PFS is assessed by response assessment in neuro-oncology high-grade glioma criteria (RANO-HGG) by blind independent central review. Secondary objectives include safety, additional efficacy endpoints, clinical benefit, and quality of life. Eligible patients have histologically confirmed H3 K27M-mutant diffuse glioma, a Karnofsky/Lansky performance status ≥70, and completed first-line radiotherapy. Eligibility is not restricted by age; however, patients must be ≥10 kg at time of randomization. Patients with a primary spinal tumor, diffuse intrinsic pontine glioma, leptomeningeal disease, or cerebrospinal fluid dissemination are not eligible. ACTION is currently enrolling in multiple international sites., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)
Published: 2024
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

164 results on '"T. Cloughesy"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources