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Expert Opinion on Therapeutic Targets Volume 13, 2009 - Issue 4
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Reviews

Anti-VEGF therapies for malignant glioma: treatment effects and escape mechanisms

Hrvoje Miletic University of Bergen, NorLux Neuro-Oncology, Department of Biomedicine, Jonas Lies vei 91, N 5009, Bergen, Norway +47 55 58 6736; +47 55 58 6360; [email protected]
,
Simone P Niclou NorLux Neuro-Oncology Laboratory, CRP-Santé, Luxembourg
,
Mikael Johansson NorLux Neuro-Oncology Laboratory, CRP-Santé, Luxembourg; Umeå University, Department of Oncology, Sweden
&
Rolf Bjerkvig University of Bergen, NorLux Neuro-Oncology, Department of Biomedicine, Jonas Lies vei 91, N 5009, Bergen, Norway +47 55 58 6736; +47 55 58 6360; [email protected]; NorLux Neuro-Oncology Laboratory, CRP-Santé, Luxembourg
Pages 455-468 | Published online: 31 Mar 2009

Bibliography

  • Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 2007;114(2):97-109
  • Wen PY, Kesari S. Malignant gliomas in adults. N Engl J Med 2008;359(5):492-507
  • Wrensch M, Minn Y, Chew T, et al. Epidemiology of primary brain tumors: current concepts and review of the literature. Neuro Oncol 2002;4(4):278-99
  • Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005;352(10):987-96
  • Sathornsumetee S, Rich JN. Antiangiogenic therapy in malignant glioma: promise and challenge. Curr Pharm Des 2007;13(35):3545-58
  • Holash J, Maisonpierre PC, Compton D, et al. Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science 1999;284(5422):1994-8
  • Leenders WP, Kusters B, de Waal RM. Vessel co-option: how tumors obtain blood supply in the absence of sprouting angiogenesis. Endothelium 2002;9(2):83-7
  • Sakariassen PO, Prestegarden L, Wang J, et al. Angiogenesis-independent tumor growth mediated by stem-like cancer cells. Proc Natl Acad Sci USA 2006;103(44):16466-71
  • Jain RK, di Tomaso E, Duda DG, et al. Angiogenesis in brain tumours. Nat Rev Neurosci 2007;8(8):610-22
  • Plate KH, Breier G, Millauer B, et al. Up-regulation of vascular endothelial growth factor and its cognate receptors in a rat glioma model of tumor angiogenesis. Cancer Res 1993;53(23):5822-7
  • Plate KH, Risau W. Angiogenesis in malignant gliomas. Glia 1995;15(3):339-47
  • Duda DG, Cohen KS, Kozin SV, et al. Evidence for incorporation of bone marrow-derived endothelial cells into perfused blood vessels in tumors. Blood 2006;107(7):2774-6
  • Santarelli JG, Udani V, Yung YC, et al. Incorporation of bone marrow-derived Flk-1-expressing CD34+ cells in the endothelium of tumor vessels in the mouse brain. Neurosurgery 2006;59(2):374-82; discussion-82
  • Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature 2000;407(6801):249-57
  • Yano S, Shinohara H, Herbst RS, et al. Expression of vascular endothelial growth factor is necessary but not sufficient for production and growth of brain metastasis. Cancer Res 2000;60(17):4959-67
  • Folberg R, Hendrix MJ, Maniotis AJ. Vasculogenic mimicry and tumor angiogenesis. Am J Pathol 2000;156(2):361-81
  • McDonald DM, Munn L, Jain RK. Vasculogenic mimicry: how convincing, how novel, and how significant? Am J Pathol 2000;156(2):383-8
  • Zhang S, Zhang D, Sun B. Vasculogenic mimicry: current status and future prospects. Cancer Lett 2007;254(2):157-64
  • Yue WY, Chen ZP. Does vasculogenic mimicry exist in astrocytoma? J Histochem Cytochem 2005;53(8):997-1002
  • Roy H, Bhardwaj S, Yla-Herttuala S. Biology of vascular endothelial growth factors. FEBS Lett 2006;580(12):2879-87
  • Senger DR, Galli SJ, Dvorak AM, et al. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 1983;219(4587):983-5
  • Keck PJ, Hauser SD, Krivi G, et al. Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science 1989;246(4935):1309-12
  • Leung DW, Cachianes G, Kuang WJ, et al. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 1989;246(4935):1306-9
  • Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med 2003;9(6):669-76
  • Houck KA, Ferrara N, Winer J, et al. The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA. Mol Endocrinol 1991;5(12):1806-14
  • Tischer E, Mitchell R, Hartman T, et al. The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem 1991;266(18):11947-54
  • Robinson CJ, Stringer SE. The splice variants of vascular endothelial growth factor (VEGF) and their receptors. J Cell Sci 2001;114(Pt 5):853-65
  • Plate KH. Mechanisms of angiogenesis in the brain. J Neuropathol Exp Neurol 1999;58(4):313-20
  • Plate KH, Breier G, Weich HA, Risau W. Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature 1992;359(6398):845-8
  • Shweiki D, Itin A, Neufeld G, et al. Patterns of expression of vascular endothelial growth factor (VEGF) and VEGF receptors in mice suggest a role in hormonally regulated angiogenesis. J Clin Invest 1993;91(5):2235-43
  • Rak J, Yu JL. Oncogenes and tumor angiogenesis: the question of vascular “supply” and vascular “demand”. Semin Cancer Biol 2004;14(2):93-104
  • Pal S, Datta K, Mukhopadhyay D. Central role of p53 on regulation of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) expression in mammary carcinoma. Cancer Res 2001;61(18):6952-7
  • Zhang L, Yu D, Hu M, et al. Wild-type p53 suppresses angiogenesis in human leiomyosarcoma and synovial sarcoma by transcriptional suppression of vascular endothelial growth factor expression. Cancer Res 2000;60(13):3655-61
  • Ohh M, Kaelin WG Jr. The von Hippel-Lindau tumour suppressor protein: new perspectives. Mol Med Today 1999;5(6):257-63
  • Cohen T, Nahari D, Cerem LW, et al. Interleukin 6 induces the expression of vascular endothelial growth factor. J Biol Chem 1996;271(2):736-41
  • Pertovaara L, Kaipainen A, Mustonen T, et al. Vascular endothelial growth factor is induced in response to transforming growth factor-β in fibroblastic and epithelial cells. J Biol Chem 1994;269(9):6271-4
  • Tsai JC, Goldman CK, Gillespie GY. Vascular endothelial growth factor in human glioma cell lines: induced secretion by EGF, PDGF-BB, and bFGF. J Neurosurg 1995;82(5):864-73
  • Samoto K, Ikezaki K, Ono M, et al. Expression of vascular endothelial growth factor and its possible relation with neovascularization in human brain tumors. Cancer Res 1995;55(5):1189-93
  • Schmidt NO, Westphal M, Hagel C, et al. Levels of vascular endothelial growth factor, hepatocyte growth factor/scatter factor and basic fibroblast growth factor in human gliomas and their relation to angiogenesis. Int J Cancer 1999;84(1):10-8
  • Brown LF, Berse B, Jackman RW, et al. Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in breast cancer. Hum Pathol 1995;26(1):86-91
  • Guidi AJ, Abu-Jawdeh G, Berse B, et al. Vascular permeability factor (vascular endothelial growth factor) expression and angiogenesis in cervical neoplasia. J Natl Cancer Inst 1995;87(16):1237-45
  • Wong MP, Cheung N, Yuen ST, et al. Vascular endothelial growth factor is up-regulated in the early pre-malignant stage of colorectal tumour progression. Int J Cancer 1999;81(6):845-50
  • Nagy JA, Benjamin L, Zeng H, et al. Vascular permeability, vascular hyperpermeability and angiogenesis. Angiogenesis 2008;11(2):109-19
  • Kaal EC, Vecht CJ. The management of brain edema in brain tumors. Curr Opin Oncol 2004;16(6):593-600
  • Brown LF, Detmar M, Claffey K, et al. Vascular permeability factor/vascular endothelial growth factor: a multifunctional angiogenic. cytokine Exs 1997;79:233-69
  • Dvorak HF, Brown LF, Detmar M, Dvorak AM. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol 1995;146(5):1029-39
  • Ferrara N. Molecular and biological properties of vascular endothelial growth factor. J Mol Med 1999;77(7):527-43
  • Benjamin LE, Golijanin D, Itin A, et al. Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal. J Clin Invest 1999;103(2):159-65
  • Shibuya M. Vascular endothelial growth factor receptor-1 (VEGFR-1/Flt-1): a dual regulator for angiogenesis. Angiogenesis 2006;9(4):225-30; discussion 31
  • Lambrechts D, Storkebaum E, Carmeliet P. VEGF: necessary to prevent motoneuron degeneration, sufficient to treat ALS? Trends Mol Med 2004;10(6):275-82
  • Carmeliet P, Tessier-Lavigne M. Common mechanisms of nerve and blood vessel wiring. Nature 2005;436(7048):193-200
  • Greenberg DA, Jin K. From angiogenesis to neuropathology. Nature 2005;438(7070):954-9
  • Bielenberg DR, Pettaway CA, Takashima S, Klagsbrun M. Neuropilins in neoplasms: expression, regulation, and function. Exp Cell Res 2006;312(5):584-93
  • Pellet-Many C, Frankel P, Jia H, Zachary I. Neuropilins: structure, function and role in disease. Biochem J 2008;411(2):211-26
  • Soker S, Takashima S, Miao HQ, et al. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell 1998;92(6):735-45
  • Soker S, Miao HQ, Nomi M, et al. VEGF165 mediates formation of complexes containing VEGFR-2 and neuropilin-1 that enhance VEGF165-receptor binding. J Cell Biochem 2002;85(2):357-68
  • Ellis LM. The role of neuropilins in cancer. Mol Cancer Ther 2006;5(5):1099-107
  • Ding H, Wu X, Roncari L, et al. Expression and regulation of neuropilin-1 in human astrocytomas. Int J Cancer 2000;88(4):584-92
  • Broholm H, Laursen H. Vascular endothelial growth factor (VEGF) receptor neuropilin-1's distribution in astrocytic tumors. Apmis 2004;112(4-5):257-63
  • Hu B, Guo P, Bar-Joseph I, et al. Neuropilin-1 promotes human glioma progression through potentiating the activity of the HGF/SF autocrine pathway. Oncogene 2007;26(38):5577-86
  • Wang L, Zeng H, Wang P, et al. Neuropilin-1-mediated vascular permeability factor/vascular endothelial growth factor-dependent endothelial cell migration. J Biol Chem 2003;278(49):48848-60
  • Murga M, Fernandez-Capetillo O, Tosato G. Neuropilin-1 regulates attachment in human endothelial cells independently of vascular endothelial growth factor receptor-2. Blood 2005;105(5):1992-9
  • Pan Q, Chanthery Y, Liang WC, et al. Blocking neuropilin-1 function has an additive effect with anti-VEGF to inhibit tumor growth. Cancer Cell 2007;11(1):53-67
  • Yancopoulos GD, Davis S, Gale NW, et al. Vascular-specific growth factors and blood vessel formation. Nature 2000;407(6801):242-8
  • Reiss Y, Machein MR, Plate KH. The role of angiopoietins during angiogenesis in gliomas. Brain Pathol 2005;15(4):311-7
  • Machein MR, Knedla A, Knoth R, et al. Angiopoietin-1 promotes tumor angiogenesis in a rat glioma model. Am J Pathol 2004;165(5):1557-70
  • Sun L, Hui AM, Su Q, et al. Neuronal and glioma-derived stem cell factor induces angiogenesis within the brain. Cancer Cell 2006;9(4):287-300
  • Brat DJ, Bellail AC, Van Meir EG. The role of interleukin-8 and its receptors in gliomagenesis and tumoral angiogenesis. Neuro Oncol 2005;7(2):122-33
  • Garkavtsev I, Kozin SV, Chernova O, et al. The candidate tumour suppressor protein ING4 regulates brain tumour growth and angiogenesis. Nature 2004;428(6980):328-32
  • Bajetto A, Barbieri F, Dorcaratto A, et al. Expression of CXC chemokine receptors 1-5 and their ligands in human glioma tissues: role of CXCR4 and SDF1 in glioma cell proliferation and migration. Neurochem Int 2006;49(5):423-32
  • Rempel SA, Dudas S, Ge S, Gutierrez JA. Identification and localization of the cytokine SDF1 and its receptor, CXC chemokine receptor 4, to regions of necrosis and angiogenesis in human glioblastoma. Clin Cancer Res 2000;6(1):102-11
  • Zagzag D, Lukyanov Y, Lan L, et al. Hypoxia-inducible factor 1 and VEGF upregulate CXCR4 in glioblastoma: implications for angiogenesis and glioma cell invasion. Lab Invest 2006;86(12):1221-32
  • Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971;285(21):1182-6
  • Escudier B, Pluzanska A, Koralewski P, et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 2007;370(9605):2103-11
  • Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004;350(23):2335-42
  • Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 2007;357(26):2666-76
  • Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 2006;355(24):2542-50
  • Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007;356(2):125-34
  • Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007;356(2):115-24
  • Kim KJ, Li B, Winer J, et al. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 1993;362(6423):841-4
  • Rubenstein JL, Kim J, Ozawa T, et al. Anti-VEGF antibody treatment of glioblastoma prolongs survival but results in increased vascular cooption. Neoplasia 2000;2(4):306-14
  • Kunkel P, Ulbricht U, Bohlen P, et al. Inhibition of glioma angiogenesis and growth in vivo by systemic treatment with a monoclonal antibody against vascular endothelial growth factor receptor-2. Cancer Res 2001;61(18):6624-8
  • Ran S, Huang X, Downes A, Thorpe PE. Evaluation of novel antimouse VEGFR2 antibodies as potential antiangiogenic or vascular targeting agents for tumor therapy. Neoplasia 2003;5(4):297-307
  • de Bouard S, Herlin P, Christensen JG, et al. Antiangiogenic and anti-invasive effects of sunitinib on experimental human glioblastoma. Neuro Oncol 2007;9(4):412-23
  • Goldbrunner RH, Bendszus M, Wood J, et al. PTK787/ZK222584, an inhibitor of vascular endothelial growth factor receptor tyrosine kinases, decreases glioma growth and vascularization. Neurosurgery 2004;55(2):426-32; discussion 32
  • Jones-Bolin S, Zhao H, Hunter K, et al. The effects of the oral, pan-VEGF-R kinase inhibitor CEP-7055 and chemotherapy in orthotopic models of glioblastoma and colon carcinoma in mice. Mol Cancer Ther 2006;5(7):1744-53
  • Mendel DB, Laird AD, Xin X, et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res 2003;9(1):327-37
  • Sandstrom M, Johansson M, Andersson U, et al. The tyrosine kinase inhibitor ZD6474 inhibits tumour growth in an intracerebral rat glioma model. Br J Cancer 2004;91(6):1174-80
  • Sandstrom M, Johansson M, Bergstrom P, et al. Effects of the VEGFR inhibitor ZD6474 in combination with radiotherapy and temozolomide in an orthotopic glioma model. J Neurooncol 2008;88(1):1-9
  • Takamoto T, Sasaki M, Kuno T, Tamaki N. Flk-1 specific kinase inhibitor (SU5416) inhibited the growth of GS-9L glioma in rat brain and prolonged the survival. Kobe J Med Sci 2001;47(4):181-91
  • Vredenburgh JJ, Desjardins A, Herndon JE 2nd, et al. Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res 2007;13(4):1253-9
  • Chen W, Delaloye S, Silverman DH, et al. Predicting treatment response of malignant gliomas to bevacizumab and irinotecan by imaging proliferation with [18F] fluorothymidine positron emission tomography: a pilot study. J Clin Oncol 2007;25(30):4714-21
  • Ali SA, McHayleh WM, Ahmad A, et al. Bevacizumab and irinotecan therapy in glioblastoma multiforme: a series of 13 cases. J Neurosurg 2008;109(2):268-72
  • Norden AD, Young GS, Setayesh K, et al. Bevacizumab for recurrent malignant gliomas: efficacy, toxicity, and patterns of recurrence. Neurology 2008;70(10):779-87
  • Poulsen HS, Grunnet K, Sorensen M, et al. Bevacizumab plus irinotecan in the treatment patients with progressive recurrent malignant brain tumours. Acta Oncol 2009;48(1):52-8
  • Cloughesy T, Prados MD, Wen Y, et al. A Phase II, randomized, non-comparative clinincal 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) [abstract 2010b]. J Clin Oncol 2008;26(Suppl)
  • Glusker P, Recht L, Lane B. Reversible posterior leukoencephalopathy syndrome and bevacizumab. N Engl J Med 2006;354(9):980-2; discussion-2
  • Vredenburgh JJ, Desjardins A, Herndon JE 2nd, et al. Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol 2007;25(30):4722-9
  • Lai A, Filka E, McGibbon B, et al. Phase II pilot study of bevacizumab in combination with temozolomide and regional radiation therapy for up-front treatment of patients with newly diagnosed glioblastoma multiforme: interim analysis of safety and tolerability. Int J Radiat Oncol Biol Phys 2008;71(5):1372-80
  • Available from: http://clinicaltrials.gov
  • Wedge SR, Ogilvie DJ, Dukes M, et al. ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration. Cancer Res 2002;62(16):4645-55
  • Willett CG, Boucher Y, di Tomaso E, et al. Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med 2004;10(2):145-7
  • Batchelor TT, Sorensen AG, di Tomaso E, et al. AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell 2007;11(1):83-95
  • Jain RK. Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med 2001;7(9):987-9
  • Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 2005;307(5706):58-62
  • Ignatova TN, Kukekov VG, Laywell ED, et al. Human cortical glial tumors contain neural stem-like cells expressing astroglial and neuronal markers in vitro. Glia 2002;39(3):193-206
  • Singh SK, Clarke ID, Terasaki M, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res 2003;63(18):5821-8
  • Singh SK, Hawkins C, Clarke ID, et al. Identification of human brain tumour initiating cells. Nature 2004;432(7015):396-401
  • Hemmati HD, Nakano I, Lazareff JA, et al. Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci USA 2003;100(25):15178-83
  • Galli R, Binda E, Orfanelli U, et al. Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res 2004;64(19):7011-21
  • Leenders WP, Kusters B, Verrijp K, et al. Antiangiogenic therapy of cerebral melanoma metastases results in sustained tumor progression via vessel co-option. Clin Cancer Res 2004;10(18 Pt 1):6222-30
  • Beier D, Hau P, Proescholdt M, et al. CD133+ and CD133– glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles. Cancer Res 2007;67(9):4010-5
  • Wang J, Sakariassen PO, Tsinkalovsky O, et al. CD133 negative glioma cells form tumors in nude rats and give rise to CD133 positive cells. Int J Cancer 2008;122(4):761-8
  • Kelly PN, Dakic A, Adams JM, et al. Tumor growth need not be driven by rare cancer stem cells. Science 2007;317(5836):337
  • Lee J, Kotliarova S, Kotliarov Y, et al. Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines. Cancer Cell 2006;9(5):391-403
  • Cloughesy TF, Prados MD, Wen PY, et al. 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) [abstract 2010]. J Clin Oncol 2008;26(Suppl)
  • Sathornsumetee S, Vredenburgh JJ, Rich JN, et al. Phase II study of bevacizumab and erlotinib in patients with recurrent glioblastoma multiforme [abstract 13008]. J Clin Oncol 2008;26(Suppl)
  • Rich JN, Desjardins A, Sathornsumetee S, et al. Phase II study of bevacizumab and etoposide in patients with recurrent malignant glioma [abstract 2022]. J Clin Oncol 2008;26(Suppl)
  • Reardon DA, Fink KL, Mikkelsen T, et al. Randomized Phase II study of cilengitide, an integrin-targeting arginine-glycine-aspartic acid peptide, in recurrent glioblastoma multiforme. J Clin Oncol 2008;26(34):5610-7
  • Stupp R, Goldbrunner RH, Neyns B, et al. Phase I/IIa trial of cilengitide (EMD121974) and temozolomide with concomitant radiotherapy, followed by temozolomide and cilingitide maintenance therapy in patients with newly diagnosed glioblastoma. J Clin Oncol 2007;25(18S):2000
  • De Groot JF, Wen PY, Lamborn K, et al. Phase II single arm trial of aflibercept in patients with recurrent temozolomide-resistant glioblastoma: NABTC 0601 [abstract 2020]. J Clin Oncol 2008;26(Suppl)
  • Fine HA, Puduvalli VK, Chamberlain MC, et al. Enzastaurin versus lomustine in the treatment of recurrent, intracranial glioblastoma multiforme: a phase III study [abstract 2005]. J Clin Oncol 2008;26(Suppl)
  • Butowski NA, Lamborn K, Chang S, et al. Phase I/II study of enzastaurin plus remozolomide and radiation therapy in patients with glioblastoma multiforme or gliosarcoma [abstract 3559]. J Clin Oncol 2008;26(Suppl)
  • Chaskis C, Sadones J, Michotte A, et al. A Phase II trial of sunitib in patients with recurrent high-grade glioma [abstract 13001]. J Clin Oncol 2008;26(Suppl)

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