Evolving strategies: Future treatment of glioblastoma

Expert Review of Neurotherapeutics

Volumn 11, Issue 4, 2011, Pages 519-532

  Chamberlain, Marc ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

Author keywords

alkylator based chemotherapy; angiogenesis; chemoradiotherapy; cytotoxic agents; GBM; glioblastoma; targeted therapy; temozolomide; vascular endothelial growth factor; VEGF

Indexed keywords

AXITINIB; BEVACIZUMAB; CDX 110; CEDIRANIB; CILENGITIDE; CT 322; DASATINIB; ENZASTAURIN; ERLOTINIB; IRINOTECAN; LOMUSTINE; N ACETYLSARCOSYLGLYCYLVALYL DEXTRO ALLOISOLEUCYLTHREONYLNORVALYLISOLEUCYLARGINYLPROLINE ETHYLAMIDE; PAZOPANIB; PERIFOSINE; POLYINOSINIC POLYCYTIDYLIC ACID; RAMUCIRUMAB; RAPAMYCIN; SORAFENIB; SUNITINIB; TALAMPANEL; TAMOXIFEN; TEMOZOLOMIDE; TEMSIROLIMUS; UNCLASSIFIED DRUG; VANDETANIB; VASCULOTROPIN; VASCULOTROPIN RECEPTOR; XL 184;

ANGIOGENESIS; ANTINEOPLASTIC ACTIVITY; ARTERY EMBOLISM; BLOOD VESSEL PERMEABILITY; BRAIN HEMORRHAGE; CANCER COMBINATION CHEMOTHERAPY; CANCER GRADING; CANCER GROWTH; CANCER INHIBITION; CANCER INVASION; CANCER RADIOTHERAPY; CANCER RESISTANCE; CARCINOGENESIS; CELL CYCLE PROGRESSION; CELL MIGRATION; CELL PROLIFERATION; CELL SURVIVAL; DIGESTIVE SYSTEM PERFORATION; DRUG EFFICACY; DRUG INHIBITION; DRUG SAFETY; FOLLOW UP; GLIOBLASTOMA; HUMAN; HYPERTENSION; LOW DRUG DOSE; MULTIPLE CYCLE TREATMENT; NONHUMAN; OVERALL SURVIVAL; POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME; PROGRESSION FREE SURVIVAL; PROTEIN SYNTHESIS; PROTEINURIA; REVIEW; SIGNAL TRANSDUCTION; SURVIVAL RATE; TREATMENT DURATION; TREATMENT RESPONSE; TUMOR RECURRENCE; TUMOR VASCULARIZATION; VENOUS THROMBOEMBOLISM; WOUND HEALING;

ANGIOGENESIS INHIBITORS; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; BRAIN NEOPLASMS; DRUG RESISTANCE, NEOPLASM; GLIOBLASTOMA; GLIOMA; HUMANS; MOLECULAR TARGETED THERAPY; NEOPLASM RECURRENCE, LOCAL; PROTEIN KINASE INHIBITORS; SIGNAL TRANSDUCTION;

EID: 79953733743     PISSN: 14737175     EISSN: 17448360     Source Type: Journal    
DOI: 10.1586/ern.11.30     Document Type: Review

References (129)

1. Louis DN, Ohgaki H, Wiestler OD et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 114, 97-109 (2007). (Pubitemid 47103521)
2. Wen PY, Kesari S. Malignant gliomas in adults. N. Engl. J. Med. 359, 492-507 (2008).
3. Stupp R, Dietrich PY, Ostermann KS et al. Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide. J. Clin. Oncol. 20, 1375-1382 (2002). (Pubitemid 34177445)
4. Miletic H, Niclou SP, Johansson M, Bjerkvig R. Anti-VEGF therapies for malignant glioma: treatment effects and escape mechanisms. Expert Opin. Ther. Targets 13, 455-468 (2009).
5. Combs SE, Gutwein S, Thilmann C, Huber P, Debus J, Schulz-Ertner D. Stereotactically guided fractionated re-irradiation in recurrent glioblastoma multiforme. J. Neurooncol. 74, 167-171 (2005). (Pubitemid 41478913)
6. Maity A, Pore N, Lee J, Solomon D, O'Rourke DM. Epidermal growth factor receptor transcriptionally up-regulates vascular endothelial growth factor expression in human glioblastoma cells via a pathway involving phosphatidylinositol 3′-kinase and distinct from that induced by hypoxia. Cancer Res. 60, 5879-5886 (2000).
7. Brandes AA, Tosoni A, Franceschi E et al. Recurrence pattern after temozolomide concomitant with and adjuvant to radiotherapy in newly diagnosed patients with glioblastoma: correlation with MGMT promoter methylation status. J. Clin. Oncol. 27, 1275-1279 (2009).
8. Zuniga RM, Torcuator R, Jain R et al. Efficacy, safety and patterns of response and recurrence in patients with recurrent high-grade gliomas treated with bevacizumab plus irinotecan. J. Neurooncol. 91, 329-336 (2009).
9. Gorlia T, van den Bent MJ, Hegi ME et al. Nomograms for predicting survival of patients with newly diagnosed glioblastoma: prognostic factor analysis of EORTC and NCIC trial 26981-22981/CE.3. Lancet Oncol. 9, 29-38 (2008).
10. Stupp R, Mason WP, van den Bent MJ et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med. 352, 987-996 (2005). (Pubitemid 40349501)
11. Hegi ME, Diserens AC, Gorlia T et al. MGMT gene silencing and benefit from emozolomide in glioblastoma. N. Engl. J. ed. 352, 997-1003 (2005). (Pubitemid 40349502)
12. Rosell R, de Las PR, Balana C et al. Translational research in glioblastoma multi-forme: molecular criteria for patient election. Future Oncol. 4, 219-228 (2008). (Pubitemid 351715780)
13. Westphal M, Hilt DC, Bortey E et al. Phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary alignant glioma. Neuro. Oncol. 5, 79-88 (2003). (Pubitemid 36422560)
14. Spiegel BM, Esrailian E, Laine L, hamberlain MC. Clinical impact of djuvant chemotherapy in glioblastoma multiforme: a meta-analysis. CNS Drugs 21, 775-787 (2007). (Pubitemid 47294722)
15. Norden AD, Young GS, Setayesh K et al. Bevacizumab for recurrent malignant gliomas: efficacy, toxicity, and patterns of recurrence. Neurology 70, 779-787 (2008).
16. Wong ET, Hess KR, Gleason MJ et al. Outcomes and prognostic factors in recurrent glioma patients enrolled onto Phase II clinical trials. J. Clin. Oncol. 17, 2572-2578 (1999). (Pubitemid 29368260)
17. Ballman KV, Buckner JC, Brown PD et al. The relationship between six-month progression-free survival and 12-month overall survival end points for Phase II trials in patients with glioblastoma multiforme. Neuro. Oncol. 9, 29-38 (2007). (Pubitemid 46543486)
18. Lamborn KR, Yung WK, Chang SM et al. Progression-free survival: an important end point in evaluating therapy for recurrent high-grade gliomas. Neuro. Oncol. 10, 162-170 (2008).
19. Idbaih A, Ducray F, Sierra DR, Hoang-Xuan K, Delattre JY. Therapeutic application of noncytotoxic molecular targeted therapy in gliomas: growth factor receptors and angiogenesis inhibitors. Oncologist 13, 978-992 (2008).
20. Kreisl TN, Kim L, Moore K et al. Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J. Clin. Oncol. 27, 740-745 (2009).
21. Friedman HS, Prados MD, Wen PY et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J. Clin. Oncol. 27, 4733-4740 (2009).
22. Sul J, Panageas KS, Lassman AB et al. A randomized Phase II trial of concurrent temozolomide (TMZ) and radiotherapy (RT) followed by dose dense compared to metronomic TMZ and maintenance cis-retinoic acid for patients with newly diagnosed glioblastoma multiforme (GBM). J. Clin. Oncol. 25 (S18), Abstract 2031 (2007).
23. Alnaami IM, Mehta V, Gourishnkar S, Senthilselvan A. Evaluation of concomitant temozolomide and radiotherapy treatment in patients with glioblastoma multiforme in two Canadian tertiary care centers. Neuro. Oncol. 11(5), 583 (2009).
24. Wick A, Pascher C, Wick W et al. Rechallenge with temozolomide in patients with recurrent gliomas. J. Neurol. 256, 734-741 (2009).
25. Perry JR, Rizek P, Cashman R, Morrison M, Morrison T. Temozolomide rechallenge in recurrent malignant glioma by using a continuous temozolomide schedule: the 'rescue' approach. Cancer 113, 2152-2157 (2008).
26. Brada M, Stenning S, Gabe R et al. Temozolomide versus procarbazine, lomustine and vincristine in recurrent high-grade glioma. J. Clin. Oncol. 28, 4601-4608 (2010).
27. Pennell NA, Lynch TJ Jr. Combined inhibition of the VEGFR and EGFR signaling pathways in the treatment of NSCLC. Oncologist 14, 399-411 (2009).
28. Ferrara N. Molecular and biological properties of vascular endothelial growth factor. J. Mol. Med. 77, 527-543 (1999). (Pubitemid 29426311)
29. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat. Med. 9, 669-676 (2003). (Pubitemid 36749215)
30. Goudar RK, Vlahovic G. Hypoxia, angiogenesis, and lung cancer. Curr. Oncol. Rep. 10, 277-282 (2008).
31. Morabito A, De Maio E, Di Maio M, Normanno N, Perrone F. Tyrosine kinase inhibitors of vascular endothelial growth factor receptors in clinical trials: current status and future directions. Oncologist 11, 753-764 (2006). (Pubitemid 44157563)
32. Kowanetz M, Ferrara N. Vascular endothelial growth factor signaling pathways: therapeutic perspective. Clin. Cancer Res. 12, 5018-5022 (2006). (Pubitemid 44453326)
33. Kiselyov A, Balakin KV, Tkachenko SE. VEGF/VEGFR signalling as a target for inhibiting angiogenesis. Expert Opin. Investig. Drugs 16, 83-107 (2007). (Pubitemid 44964169)
34. Schneider BP, Sledge GW Jr. Drug insight: VEGF as a therapeutic target for breast cancer. Nat. Clin. Pract. Oncol. 4, 181-189 (2007). (Pubitemid 46358855)
35. Fontanini G, Vignati S, Boldrini L et al. Vascular endothelial growth factor is associated with neovascularization and influences progression of non-small cell lung carcinoma. Clin. Cancer Res. 3, 861-865 (1997). (Pubitemid 27252933)
36. Fontanini G, Faviana P, Lucchi M et al. A high vascular count and overexpression of vascular endothelial growth factor are associated with unfavourable prognosis in operated small cell lung carcinoma. Br. J. Cancer 86, 558-563 (2002). (Pubitemid 34185092)
37. Greten TF, Korangy F, Manns MP, Malek NP. Molecular therapy for the treatment of hepatocellular carcinoma. Br. J. Cancer 100, 19-23 (2009).
38. Skelton MR, O'Neil B. Targeted therapies for hepatocellular carcinoma. Clin. Adv. Hematol. Oncol. 6, 209-218 (2008). (Pubitemid 351516208)
39. Shahi PK, Lovelle AS, Manga GP. Tumoral angiogenesis and breast cancer. Clin. Transl. Oncol. 11, 138-142 (2009).
40. Lennard CM, Patel A, Wilson J et al. Intensity of vascular endothelial growth factor expression is associated with increased risk of recurrence and decreased disease-free survival in papillary thyroid cancer. Surgery 129, 552-558 (2001). (Pubitemid 32374986)
41. Klein M, Picard E, Vignaud JM et al. Vascular endothelial growth factor gene and protein: strong expression in thyroiditis and thyroid carcinoma. J. Endocrinol. 161, 41-49 (1999). (Pubitemid 29170190)
42. Oka N, Soeda A, Inagaki A et al. VEGF promotes tumorigenesis and angiogenesis of human glioblastoma stem cells. Biochem. Biophys. Res. Commun. 360, 553-559 (2007). (Pubitemid 47048135)
43. Bahleda R, Soria J, Harbison C et al. Tumor regression and pharmacodynamic (PD) biomarker validation in non-small cell lung cancer (NSCLC) patients treated with the ErbB/VEGFR inhibitor BMS-690514. J. Clin. Oncol. 27(S15), Abstract 8098 (2009).
44. Nam DH, Park K, Suh YL, Kim JH. Expression of VEGF and brain specific angiogenesis inhibitor-1 in glioblastoma: prognostic significance. Oncol. Rep. 11, 863-869 (2004).
45. Kong DS, Song SY, Kim DH et al. Prognostic significance of c-Met expression in glioblastomas. Cancer 115, 140-148 (2009).
46. Comoglio PM, Giordano S, Trusolino L. Drug development of MET inhibitors: targeting oncogene addiction and expedience. Nat. Rev. Drug Discov. 7, 504-516 (2008). (Pubitemid 351767118)
47. Natale RB, Bodkin D, Govindan R et al. Vandetanib versus gefitinib in patients with advanced non-small-cell lung cancer: results from a two-part, double-blind, randomized Phase II study. J. Clin. Oncol. 27, 2523-2529 (2009).
48. Herbst R, Sun Y, Korfee S et al. Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small cell lung cancer (NSCLC): a randomized, double-blind Phase III trial (ZODIAC). J. Clin. Oncol. 27(18 Suppl.), Abstract CRA8003 (2009).
49. Llovet JM, Ricci S, Mazzaferro V et al. Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med. 359, 378-390 (2008).
50. Bergers G, Hanahan D. Modes of resistance to anti-angiogenic therapy. Nat. Rev. Cancer 8, 592-603 (2008).
51. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature 407, 249-257 (2000).
52. Folkman J. What is the evidence that tumors are angiogenesis dependent? J. Natl Cancer Inst. 82, 4-6 (1990). (Pubitemid 20020880)
53. Horn L, Sandler A. Angiogenesis in the treatment of non-small cell lung cancer. Proc. Am. Thorac. Soc. 6, 206-217 (2009).
54. Sathornsumetee S, Rich JN. Antiangiogenic therapy in malignant glioma: promise and challenge. Curr. Pharm. Des. 13, 3545-3558 (2007). (Pubitemid 350238925)
55. Sathornsumetee S, Reardon DA, Desjardins A, Quinn JA, Vredenburgh JJ, Rich JN. Molecularly targeted therapy for malignant glioma. Cancer 110, 13-24 (2007).
56. Roberts WG, Delaat J, Nagane M, Huang S, Cavenee WK, Palade GE. Host microvasculature influence on tumor vascular morphology and endothelial gene expression. Am. J. Pathol. 153, 1239-1248 (1998). (Pubitemid 28465847)
57. Takano S, Yoshii Y, Kondo S et al. Concentration of vascular endothelial growth factor in the serum and tumor tissue of brain tumor patients. Cancer Res. 56, 2185-2190 (1996). (Pubitemid 26119923)
58. Calabrese C, Poppleton H, Kocak M. A perivascular niche for brain tumor stem cells. Cancer Cell. 11, 69-82 (2007). (Pubitemid 46054518)
59. Peles E, Lidar Z, Simon AJ, Grossman R, Nass D, Ram Z. Angiogenic factors in the cerebrospinal fluid of patients with astrocytic brain tumors. Neurosurgery 55, 562-567 (2004). (Pubitemid 39186844)
60. Quesada AR, Medina MA, Alba E. Playing only one instrument may be not enough: limitations and future of the antiangiogenic treatment of cancer. Bioessays 29, 1159-1168 (2007). (Pubitemid 350057387)
61. Ferrara N, Gerber HP. The role of vascular endothelial growth factor in angiogenesis. Acta Haematol. 106, 148-156 (2001). (Pubitemid 34124153)
62. Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr. Rev. 18, 4-25 (1997). (Pubitemid 27076453)
63. Cao Y, Liu Q. Therapeutic targets of multiple angiogenic factors for the treatment of cancer and metastasis. Adv. Cancer Res. 97, 203-224 (2007). (Pubitemid 46528989)
64. Goldfarb M. The fibroblast growth factor family. Cell Growth Differ. 1, 439-445 (1990).
65. Prat A, Casado E, Cortes J. New approaches in angiogenic targeting for colorectal cancer. World J. Gastroenterol. 13, 5857-5866 (2007). (Pubitemid 350148502)
66. Tortora G, Ciardiello F, Gasparini G. Combined targeting of EGFR-dependent and VEGF-dependent pathways: rationale, preclinical studies and clinical applications. Nat. Clin. Pract. Oncol. 5, 521-530 (2008).
67. Herbst RS, Johnson DH, Mininberg E et al. Phase I/II trial evaluating the anti-vascular endothelial growth factor monoclonal antibody bevacizumab in combination with the HER-1/epidermal growth factor receptor tyrosine kinase inhibitor erlotinib for patients with recurrent non-small-cell lung cancer. J. Clin. Oncol. 23, 2544-2555 (2005).
68. Tabernero J. The role of VEGF and EGFR inhibition: implications for combining anti-VEGF and anti-EGFR agents. Mol. Cancer Res. 5, 203-220 (2007). (Pubitemid 46569773)
69. Ciardiello F, Troiani T, Bianco R et al. Interaction between the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor (VEGF) pathways: a rational approach for multi-target anticancer therapy. Ann. Oncol. 17(Suppl. 7), vii109-vii114 (2006). (Pubitemid 43985191)
70. You WK, Falcon B, Hashizume H et al. Exaggerated regression of blood vessels, hypoxia, and apoptosis in tumors after c-Met and VEGFR inhibition. J. Clin. Invest. (2011) (In press).
71. Li Y, Guessous F, DiPierro C. Interactions between PTEN and the c-Met pathway in glioblastoma and implications for therapy. Mol. Cancer Ther. 8, 376-385 (2009).
72. Martens T, Schmidt NO, Eckerich C et al. A novel one-armed anti-c-Met antibody inhibits glioblastoma growth in vivo. Clin. Cancer Res. 12, 6144-6152 (2006). (Pubitemid 44703780)
73. Chu SH, Feng DF, Zhang H et al. c-Met-targeted RNA interference inhibits growth and metastasis of glioma U251 cells in vitro. J. Neurooncol. 93, 183-189 (2009).
74. Santarpia L, Ye L, Gagel RF. Beyond RET: potential therapeutic approaches for advanced and metastatic medullary thyroid carcinoma. J. Intern. Med. 266, 99-113 (2009).
75. Jeffers M, Fiscella M, Webb CP et al. The mutationally activated MET receptor mediates motility and metastasis. Proc. Natl Acad. Sci. USA 95, 14417-14422 (1998). (Pubitemid 28549382)
76. Giordano S, Bardelli A, Zhen Z, Menard S, Ponzetto C, Comoglio PM. A point mutation in the MET oncogene abrogates metastasis without affecting transformation. Proc. Natl Acad. Sci. USA 94, 13868-13872 (1997). (Pubitemid 28009676)
77. 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 84, 10-18 (1999). (Pubitemid 29059101)
78. Bean J, Brennan C, Shih JY et al. MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc. Natl Acad. Sci. USA 104, 20932-20937 (2007).
79. Chu SH, Zhu ZA, Yuan XH, Li ZQ, Jiang PC. In vitro and in vivo potentiating the cytotoxic effect of radiation on human U251 gliomas by the c-Met antisense oligodeoxynucleotides. J. Neurooncol. 80, 143-149 (2006).
80. Ebos JM, Lee CR, Cruz-Munoz W, Bjarnason GA, Christensen JG, Kerbel RS. Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell 15, 232-239 (2009).
81. Loges S, Mazzone M, Hohensinner P, Carmeliet P. Silencing or fueling metastasis with VEGF inhibitors: antiangiogenesis revisited. Cancer Cell 15, 167-170 (2009).
82. Pennacchietti S, Michieli P, Galluzzo M, Mazzone M, Giordano S, Comoglio PM. Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene. Cancer Cell 3, 347-361 (2003). (Pubitemid 38340304)
83. Jain RK, Duda DG, Willett CG et al. Biomarkers of response and resistance to antiangiogenic therapy. Nat. Rev. Clin. Oncol. 6, 327-338 (2009).
84. Paez-Ribes M, Allen E, Hudock J et al. Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell 15, 220-231 (2009).
85. Kamoun WS, Ley CD, Farrar CT et al. Edema control by cediranib, a vascular endothelial growth factor receptor-targeted kinase inhibitor, prolongs survival despite persistent brain tumor growth in mice. J. Clin. Oncol. 27, 2542-2552 (2009).
86. Pope WB, Xia Q, Paton VE et al. Patterns of progression in patients with recurrent glioblastoma treated with bevacizumab. Neurology 76, 432-437 (2011).
87. Wick A, Dorner N, Schafer N et al. Bevacizumab does not increase the risk of remote relapse in malignant glioma. Ann. Neurol. (2011) (In press).
88. Chamberlain MC. Radiographic patterns of relapse in glioblastoma. J. Neurooncol. 101(2), 319-323 (2011).
89. Banerjee S, Dowsett M, Ashworth A, Martin LA. Mechanisms of disease: angiogenesis and the management of breast cancer. Nat. Clin. Pract. Oncol. 4(9), 536-550 (2007). (Pubitemid 47351464)
90. Fox SB, Generali DG, Harris AL. Breast tumour angiogenesis. Breast Cancer Res. 9, 216 (2007).
91. Grose R, Dickson C. Fibroblast growth factor signaling in tumorigenesis. Cytokine Growth Factor Rev. 16, 179-186 (2005). (Pubitemid 40616115)
92. van Linde ME, Verhoeff JJC, Stalpers LJA, Reijneveld JC, Richel DJ, Van Furth WR. Feasibility of combined treatment with bevacizumab radiotherapy and temozolomide in resectable and unresectable newly diagnosed glioblastoma multiforme. Neuro. Oncol. 11(5), 563-699 (2009).
93. Hofland KF, Poulsen HS, Sorensen MP et al. First-line therapy with bevacizumab and irinotecan versus bevacizumab and temozolomide and delayed concomitant radiotherapy in newly diagnosed primary glioblastoma multiforme: early results from a randomized Phase II study. Neuro. Oncol. 11(5), 620 (2009).
94. Lai A, Nghiemphu P, Pope W, et al. Phase II study of bevacizumab plus temozolomide during and after radiotherapy for patients with newly diagnosed glioblastoma multiforme. J. Clin. Oncol. 29(2), 142-148 (2011).
95. Desjardins A, Reardon DA, Peters KB et al. Bevacizumab (BV) in combination to temozolomide (TMZ) and radiation therapy (RT) followed by BV, TMZ, and irinotecan (CPT-11) for newly diagnosed glioblastoma multiforme (GBM): a Phase 2 trial. Neuro. Oncol. 11(5), 634 (2009).
96. Gruber ML, Raza S, Gruber D, Narayana A. Bevacizumab in combination with radiotherapy plus concomitant and adjuvant temozolomide for newly diagnosed glioblastoma: update progression-free survival, overall survival, and toxicity. J. Clin. Oncol. 27(15S), Abstract 2017 (2009).
97. Peters K, Desjardins A, Reardon DA et al. Temozolomide (TMZ) and bevacizumab (BV) as initial treatment for unresectable or multifocal glioblastoma multiforme (GBM). J. Clin. Oncol. 27(Suppl.), e13025 (2009).
98. Chinot O, de La Motte Rouge T, Zeaiter A et al. Preclinical and clinical rationale for a Phase III trial of bevacizumab combined with the current standard of care in patients with newly diagnosed glioblastoma multiforme. Neuro. Oncol. 11(5), 628 (2009).
99. Reardon DA, Fink KL, Mikkelsen T et al. Randomized Phase II study of cilengitide, an integrin-targeting arginine-glycineaspartic acid peptide, in recurrent glioblastoma multiforme. J. Clin. Oncol. 26, 5610-5617 (2008).
100. Stupp R, Goldbrunner R, Neyns B et al. Phase I/IIa trial of cilengitide (EMD121974) and temozolomide with concomitant radiotherapy, followed by temozolomide and cilengitide maintenance therapy in patients with newly diagnosed glioblastoma. J. Clin. Oncol. 25(18S), Abstract 2000 (2007).
101. Lamar RE, Spigel DR, Burris HA et al. Phase II trial of radiation therapy/temozolomide followed by temozolomide/sorafenib in the first-line treatment of glioblastoma multiforme (GBM). J. Clin. Oncol. 27(15S), Abstract 2018 (2009).
102. Brown PD, Krishnan S, Sarkaria JN et al. Phase I/II trial of erlotinib and temozolomide with radiation therapy in the treatment of newly diagnosed glioblastoma multiforme: North Central Cancer Treatment Group Study N0177. J. Clin. Oncol. 26, 5603-5609 (2008).
103. Prados MD, Chang SM, Butowski N et al. Phase II study of erlotinib plus temozolomide during and after radiation therapy in patients with newly diagnosed glioblastoma multiforme or gliosarcoma. J. Clin. Oncol. 27, 579-584 (2009).
104. Heimberger AB, Archer GE, Mitchell DA et al. Epidermal growth factor receptor variant II (EGFRvIII) vaccine (CDX-110) in GBM. J. Clin. Oncol. 27(15S), Abstract 2021 (2009).
105. Sampson JH, heimberger AB, Archer GE et al. Immunologic escape after prolonged progression-free survival with epidermal growth factor receptor variant III peptide vaccination in patients with newly diagnosed glioblastoma. J. Clin. Oncol. 31, 4722-4729 (2010).
106. Rosenfeld MR, Chamberlain M, Grossman SA et al. A Phase II study of chemoradiation followed by adjuvant temozolomide and poly-ICLC in patients with newly diagnosed glioblastoma: 12-and 18-month survival data (NABTT 0501) [abstract]. J. Clin. Oncol. 27(15S), Abstract 2002 (2009).
107. Grossman SA, Ye X, Chamberlain M et al. Talampanel with standard radiation and temozolomide in patients with newly diagnosed glioblastoma: a multicenter Phase II trial. J. Clin. Oncol. 27, 4155-4161 (2009).
108. Takano T, Lin JH, Arcuino G, Gao Q, Yang J, Nedergaard M. Glutamate release promotes growth of malignant gliomas. Nat. Med. 7, 1010-1015 (2001). (Pubitemid 32937380)
109. Yoshida Y, Tsuzuki K, Ishiuchi S, Ozawa S. Serum-dependence of AMPA receptormediated proliferation in glioma cells. Pathol. Int. 56, 262-271 (2006).
110. Lyons SA, Chung WJ, Weaver AK, Ogunrinu T, Sontheimer H. Autocrine glutamate signaling promotes glioma cell invasion. Cancer Res. 67, 9463-9471 (2007). (Pubitemid 47535936)
111. Hurwitz HI, Fehrenbacher L, Hainsworth JD et al. Bevacizumab in combination with fluorouracil and leucovorin: an active regimen for first-line metastatic colorectal cancer. J. Clin. Oncol. 23, 3502-3508 (2005).
112. Kerr C. Bevacizumab and chemotherapy improves survival in NSCLC. Lancet Oncol. 6, 266 (2005). (Pubitemid 40590259)
113. Vredenburgh JJ, Desjardins A, Herndon JE et al. Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J. Clin. Oncol. 25, 4722-4729 (2007). (Pubitemid 350086473)
114. Gilbert MR, Wang M, Aldape K et al. RTOG 0625: a Phase II study of bevacizumab with irinotecan in recurrent glioblastoma (GBM). J. Clin. Oncol. 27(15S), Abstract 2011 (2009).
115. Stankewitz S, Dresemann G. Addition of continuous low dose temozolomide to bevacizumab plus irinotecan after bevacizumab plus irinotecan failure in heavily pretreated glioblastoma multiforme (GBM). J. Clin. Oncol. 27(Suppl.), e13015 (2009).
116. 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 11, 83-95 (2007). (Pubitemid 46075199)
117. Sennino B. Inhibition of tumor invasiveness by c-Met/VEGFR blockade. Presented at: Gordon Research Conference: Angiogenesis, RI, USA, 2-7 August 2009.
118. de Groot JF, Prados M, Urquhart T et al. A Phase II study of XL184 in patients (pts) with progressive glioblastoma multiforme (GBM) in first or second relapse. J. Clin. Oncol. 27(15S), Abstract 2047 (2009).
119. Wen PY, Cloughesy T, Kuhn J et al. Phase I/II study of sorafenib and temsiroliums for patients with recurrent glioblastoma (GBM) (NABTC 05-02) [abstract]. J. Clin. Oncol. 27(15S), Abstract 2006 (2009).
120. Chaskis C, Dujardin M, Michotte A, Neyns B. Evaluation of the early antiangiogenic activity of sunitinib malate by perfusion of CBF and CBV values from DSC-based perfusion in recurrent glioblastoma. Neuro. Oncol. 10, 1062 (2008).
121. Neyns B, Chaskis C, Dujardin M et al. Phase II trial of sunitinib malate in patients with temozolomide refractory recurrent high-grade glioma. J. Clin. Oncol. 27(15S), Abstract 2038 (2009).
122. van den Bent MJ, Brandes AA, Rampling R et al. Randomized Phase II trial of erlotinib versus temozolomide or carmustine in recurrent glioblastoma: EORTC brain tumor group study 26034. J. Clin. Oncol. 27, 1268-1274 (2009).
123. Chang SM, Kuhn J, Lamborn K et al. Phase I/II study of erlotinib and temsirolimus for patients with recurrent malignant gliomas (MG) (NABTC 04-02). J. Clin. Oncol. 27(15S), Abstract 2004 (2009).
124. Wick W, Puduvalli VK, Chamberlain MC et al. Phase III study of enzastaurin compared with lomustine in the treatment of recurrent intracranial glioblastoma. J. Clin. Oncol. 28, 1168-1174 (2010).
125. Wick W, Puduvalli VK, Chamberlain M et al. Enzastaurin (ENZ) versus lomustine (CCNU) in the treatment of recurrent, intracranial glioblastoma (GBM): a Phase III study. Neuro. Oncol. 10, Abstract 022 (2008).
126. Kerbel RS. Tumor angiogenesis. N. Engl. J. Med. 358, 2039-2049 (2008). (Pubitemid 351656458)
127. Fojo T. Commentary: novel therapies for cancer: why dirty might be better. Oncologist 13, 277-283 (2008). (Pubitemid 351679902)
128. Nabors LB, Mikkelsen T, Batchelor T et al. NABTT 0306: a randomized Phase II trial of EMD 121974 in conjunction with concomitant and adjuvant temozolomide with radiation therapy in patients with newly diagnosed glioblastoma multiforme (GBM). J. Clin. Oncol. 27(15S), Abstract 2001 (2009).
129. Nabors LB, Fiveash JB, Markert JM et al. A Phase 1 trial of ABT-510 concurrent with standard chemoradiation for patients with newly diagnosed glioblastoma. Arch. Neurol. 67, 313-319 (2010).