Insights into pharmacotherapy of malignant glioma in adults

Expert Opinion on Pharmacotherapy

Volumn 10, Issue 14, 2009, Pages 2279-2290

  Salvati, Maurizio ^a   D'Elia, Alessandro ^a,b   Formichella, Anna Isabella ^a,b   Frati, Alessandro ^a  

^a IRCCS NEUROMED   (Italy)

^b SAPIENZA UNIVERSITY OF ROME   (Italy)

Author keywords

Bevacizumab; Chemotherapy; Erlotinib; Glioblastoma; Grade 3 gliomas; Temozolomide

Indexed keywords

AFLIBERCEPT; BEVACIZUMAB; CARMUSTINE; CEDIRANIB; CELECOXIB; CILENGITIDE; DENDRITIC CELL VACCINE; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR; ERLOTINIB; FLUORODEOXYGLUCOSE F 18; FOTEMUSTINE; GEFITINIB; IRINOTECAN; LOMUSTINE; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; METHYLATED DNA PROTEIN CYSTEINE METHYLTRANSFERASE; POLYMER; PROCARBAZINE; RAPAMYCIN; ROFECOXIB; TAMOXIFEN; TEMOZOLOMIDE; VASCULOTROPIN; VASCULOTROPIN INHIBITOR; VINCRISTINE;

ADD ON THERAPY; ADJUVANT THERAPY; ANTINEOPLASTIC ACTIVITY; ASTROCYTOMA; BINDING AFFINITY; BLOOD TOXICITY; BRAIN HEMORRHAGE; BRAIN METASTASIS; BREAST CANCER; CANCER ADJUVANT THERAPY; CANCER COMBINATION CHEMOTHERAPY; CANCER MORTALITY; CANCER PATIENT; CANCER RADIOTHERAPY; CANCER SURGERY; CANCER SURVIVAL; CHROMOSOME DELETION; CLINICAL PROTOCOL; CLINICAL TRIAL; COLORECTAL CANCER; CONTINUOUS INFUSION; CONTRAST ENHANCEMENT; DIARRHEA; DNA METHYLATION; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG CYTOTOXICITY; DRUG DELIVERY SYSTEM; DRUG EFFECT; DRUG EFFICACY; DRUG ERUPTION; DRUG HALF LIFE; DRUG MEGADOSE; DRUG METABOLISM; DRUG MONITORING; DRUG PENETRATION; DRUG POTENTIATION; DRUG PROTEIN BINDING; DRUG SAFETY; DRUG SUBSTITUTION; DRUG TOLERABILITY; DRUG WITHDRAWAL; FATIGUE; GASTROINTESTINAL TOXICITY; GENE MUTATION; GENE OVEREXPRESSION; GENETIC ANALYSIS; GLIOBLASTOMA; GLIOMA; HETEROZYGOSITY LOSS; HUMAN; HYPERTENSION; INTESTINE PERFORATION; LOW DRUG DOSE; LUNG CANCER; LYMPHOCYTOPENIA; MAXIMUM PLASMA CONCENTRATION; MOLECULAR MECHANICS; MONOTHERAPY; MULTIMODALITY CANCER THERAPY; MULTIPLE CYCLE TREATMENT; NEUROTOXICITY; NUCLEAR MAGNETIC RESONANCE IMAGING; OLIGODENDROGLIOMA; OPTIMAL DRUG DOSE; OVERALL SURVIVAL; PATIENT IDENTIFICATION; POSITRON EMISSION TOMOGRAPHY; PROGRESSION FREE SURVIVAL; PROMOTER REGION; PROTEIN DEPLETION; PROTEIN EXPRESSION; PROTEIN TARGETING; QUALITY OF LIFE; RADIATION DOSE; RADIOSENSITIZATION; REVIEW; SIGNAL TRANSDUCTION; SLOW DRUG RELEASE; THROMBOEMBOLISM; TREATMENT DURATION; TREATMENT OUTCOME; TREATMENT RESPONSE; TUMOR VASCULARIZATION;

ADULT; AGED; ANGIOGENESIS INHIBITORS; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; BRAIN NEOPLASMS; CHEMOTHERAPY, ADJUVANT; DACARBAZINE; GLIOBLASTOMA; GLIOMA; HUMANS; QUINAZOLINES;

EID: 70349384769     PISSN: 14656566     EISSN: None     Source Type: Journal    
DOI: 10.1517/14656560903146910     Document Type: Review

References (115)

1. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, editors. WHO classification of tumours of the central nervous system. IARC: Lyon, 2007
2. Walker MD, Green SB, Byar DP, et al. Randomized comparison of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery. N Engl J Med 1980;303:1323-1329 (Pubitemid 11194457)
3. Fine HA, Dear KB, Loeffler JS, et al. Meta-analysis of radiation therapy with or without adjuvant chemotherapy for malignant gliomas in adults. Cancer 1993;71:2585-2597 (Pubitemid 23100496)
4. Prados MD, Scott C, Curran WJ Jr, et al. Procarbazine, lomustine and vincristine (PCV) chemotherapy for anaplastic astrocytoma: a retrospective review of Radiation Therapy Oncology Group protocols comparing survival with carmustine or PCV adjuvant chemotherapy. J Clin Oncol 1999;17:3389-3395 (Pubitemid 29517905)
5. Medical Research Council Brain Tumour Working Party. Randomized trial of procarbazine, lomustine, and vincristine in the adjuvant treatment of high grade astrocytoma: a Medical Research Council Trial. J Clin Oncol 2001;19:509-518
6. Stewart LA. Chemotherapy in adult high grade glioma: a systematic review and meta-analysis of individual patient data from 12 randomized trials. Lancet 2002;359:1011-1018
7. Newlands ES, Stevens MF, Wedge SR, et al. Temozolomide. A review of its discovery, chemical properties, pre-clinical development and clinical trials. Cancer Treat Rev 1997;23:35-61
8. Brada M, Judson I, Beale P, et al. Phase I dose-excalation and pharmacokinetic study of temozolomide (SCH 52365) for refractory or relapsing malignancies. Br J Cancer 1999;81:1022-1030 (Pubitemid 29516147)
9. Ochs K, Kaina B. Apoptosis induced by DNA damage O6-methylguanine is Bcl-2 and caspase-9/3 regulated and Fas/caspase-8 independent. Cancer Res 2000;60:5815-5824 (Pubitemid 30808319)
10. Brada M, Hoang-Xuan K, Rampling R, et al. Multicenter phase II trial of temozolomide in patients with glioblastoma multiforme at first relapse. Ann Oncol 2001;12:259-266 (Pubitemid 32223879)
11. van den Bent M, Hegi M, Stupp R. Recent developments in the use of chemotherapy in brain tumors. Eur J Cancer 2006;42:582-588 (Pubitemid 43343679)
12. Brock CS, Newlands ES, Wedge SR, et al. Phase I trial of temozolomide using an extended continuous oral schedule. Cancer Res 1998;58:4363-4367 (Pubitemid 28450038)
13. Wedge SR, Porteous JK, Glaser MG, et al. In vitro evaluation of temozolomide combined with X-irradiation. Anticancer Drugs 1997;8:92-97
14. Van Rijn J, Heimans JJ, Van den Berg J, et al. Survival of human glioma cells treated with various combination of temozolomide and x-rays. Int J Radiat Oncol Biol Phys 2000;47:779-784 (Pubitemid 30317499)
15. Stupp R, Dietrich PY, Ostermann Kraljevic S, et al. Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide. J Clin Oncol 2002;20:1375-1382 (Pubitemid 34177445)
16. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005;352:987-996 (Pubitemid 40349501)
17. Taphoorn MJ, Stupp R, Coens C, et al. Health-related quality of life in patients with glioblastoma: a randomized controlled trial. Lancet Oncol 2005;6:937-944 (Pubitemid 41685226)
18. Stupp R, Hegi M, Mason W, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 2009;10:459-466
19. Stupp R, Hegi ME, van den Bent MJ, et al. Changing paradigms: an update on the multidisciplinary management of malignant glioma. Oncologist 2006;11:165-180 (Pubitemid 43261763)
20. Hau P, Koch D, Hundsberger T, et al. Safety and feasibility of long-term temozolomide treatment in patients with high grade glioma. Neurology 2007;68:688-690 (Pubitemid 46667817)
21. Yung WKA, Prados MD, Yaya-Tur R, et al. Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Temodal Brain Tumor Group. J Clin Oncol 1999;17:2762-2771 (Pubitemid 29415233)
22. Cairncross G, Berkey B, Shaw E, et al. Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402. J Clin Oncol 2006;24:2707-2714 (Pubitemid 46630566)
23. Van den Bent MJ, Carpentier AF, Brandes AA, et al. Adjuvant procarbazine, lomustine and vincristine improves progression-free survival but not overall survival in newly diagnosed anaplastic oligodendrogliomas: a randomized European Organization for Research and Treatment of Cancer phase III trial. J Clin Oncol 2006;24:2715-2722
24. Ochs K, Kaina B. Apoptosis induced by DNA damage O6-methylguanine is Bcl-2 and caspase-9/3 regulated and Fas/caspase-8 independent. Cancer Res 2000;60:5815-5824 (Pubitemid 30808319)
25. Gerson SL. Clinical relevance of MGMT in the treatment of cancer. J Clin Oncol 2002;20:2388-2399 (Pubitemid 34441669)
26. Gerson SL. MGMT: its role in cancer aetiology and cancer therapeutics. Nat Rev Cancer 2004;4:296-307 (Pubitemid 38525285)
27. Jagtap P, Szabo C. Poly(ADP-ribose) polymerase and the therapeutic effects of its inhibitors. Nat Rev Drug Discov 2005;4:421-440 (Pubitemid 40704125)
28. Grombacher T, Mitra S, Kaina B. Induction of alkyltransferase (MGMT) gene by DNA damaging agents and the glucocorticoid dexamethasone and comparison with the response of base excision repair genes. Carcinogenesis 1996;17:2329-2336 (Pubitemid 26402229)
29. Esteller M, Hamilton SR, Burger PC, et al. Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia. Cancer Res 1999;59:793-797 (Pubitemid 29086728)
30. Jaeckle KA, Eyre HJ, Townsend JJ, et al. Correlation of tumor O6 methylguanine DNA methyltransferase levels with survival of malignant astrocytoma patients treated with bis-chloroethylnitrosourea: a Southwest Oncology Group study. J Clin Oncol 1998;16:3310-3315
31. Friedman H, McLendon R, Kerby T, et al. DNA mismatch repair and O6-alkylguanine-DNA alkyltransferase analysis and response to temodal in newly diagnosed malignant glioma. J Clin Oncol 1998;16:3851-3857 (Pubitemid 29001538)
32. Esteller M, Garcia-Foncillas J, Andion E, et al. Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med 2000;343:1350-1354 (Pubitemid 30826035)
33. Hegi ME, Diserens AC, Godard S, et al. Clinical trial substantiates the predictive value of O6-methylguanine-DNA methyltransferase promoter methylation in glioblastoma patients treated with with temozolomide. Clin Cancer Res 2004;10:1871-1874 (Pubitemid 38375541)
34. Hegi ME, Diserens AC, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 2005;352:997-1003 (Pubitemid 40349502)
35. Eoli M, Menghi F, Bruzzone MG, et al. Methylation of O6-methylguanine DNA methyltransferase and loss of heterozigosity on 19q and/or 17p are overlapping features of secondary glioblastomas with prolonged survival. Clin Cancer Res 2007;13:2606-2613 (Pubitemid 46788026)
36. Paz MF, Yaya-Tur R, Rojas-Marcos I, et al. CpG island hypermethylation of the DNA repair enzyme methyltransferase predicts response to temozolomide in primary gliomas. Clin Cancer Res 2004;10:4933-4938 (Pubitemid 39099766)
37. Tolcher AW, Gerson SL, Denis L, et al. Marked inactivation of O6-alkylguanine-DNA alkyltransferase activity with protracted temozolomide schedules. Br J Cancer 2003;88:1004-1011 (Pubitemid 36560766)
38. Lee SM, Thatcher N, Crowther D, et al. Inactivation of O6-alkylguanine-DNA alkyltransferase in human peripheral blood mononuclear cells by temozolomide. Br J Cancer 1994;69:452-456 (Pubitemid 24076460)
39. Payne MJ, Pratap SE, Middleton MR. Temozolomide in the treatment of solid tumours: current results and rationale for dosing/scheduling. Crit Rev Oncol Hematol 2005;53:241-252
40. Hegi ME, Liu L, Herman J, et al. Correlation of O6-Methylguanine Methyltransferase (MGMT) promoter methylation with clinical outcomes in glioblastoma and clinical strategies to modulate MGMT activity. J Clin Oncol 2008;26:4189-4199
41. Wick W, Steinbach JP, Kuker WM, et al. One week on/one week off: a novel active regimen for temozolomide for recurrent glioblastoma. Neurology 2004;62:2113-2115 (Pubitemid 38738235)
42. Brandes AA, Tosoni A, Cavallo G, et al. Temozolomide 3 weeks on and 1 week off as first-line therapy for recurrent glioblastoma: phase II study from gruppo italiano cooperative di neuro-oncologia (GICNO). Br J Cancer 2006;95:1155-1160 (Pubitemid 44658477)
43. Perry JR, Mason WP, Belanger K, et al. The temozolomide RESCUE study: a phase II trial of continuous (28/28) dose-intense temozolomide (TMZ) after progression on conventional 5/28 day TMZ in patients with recurrent glioma. J Clin Oncol 2008;26:abstract 2010
44. Tosoni A, Cavallo G, Ermani M, et al. Is protracted low-dose temozolomide feasible in glioma patients? Neurology 2006;66:427-429
45. Stupp R, Hottinger AF, van den Bent MJ, et al. Frequently asked questions in the medical management of high grade glioma: a short guide with practicalanswers. Ann Oncol 2008;19(Suppl 7):vii209-16
46. Franceschi E, Omuro AM, Lassman AB, et al. Salvage temozolomide for prior temozolomide responders. Cancer 2005;104:2473-2476
47. Wick W, Platten M, Weller M. New (alternative) temozolomide regimens for the treatment of glioma. Neuro-oncol 2009;11:69-79
48. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971;285:1182-1186
49. Dietrich J, Norden A, Wen P. Emerging antiangiogenic treatments for gliomas - efficacy and safety issues. Review. Current Opin Neurol 2008;21:736-744
50. Plate KH, Breier G, Weich HA, Risau W. Vascular endothelial growth factor is a potential tumor angiogenesis factor in human gliomas in vivo. Nature 1992;359:845-848
51. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med 2003;9:669-676
52. Bao S, Wu Q, Sathornsumetee S, et al. Stem-cell like glioma cells promote tumor angiogenesis through vascular endothelial growth factor. Cancer Res 2006;66:7843-7848 (Pubitemid 44299144)
53. Stark-Vance V. Bevacizumab and CPT-11 in the treatment of relapsed malignant glioma [abstract]. In: Sixth Meeting of European Association for Neuro-Oncology. Neuro-oncol 2005;7:369
54. Pope WB, Lai A, Nghiemphu P, et al. MRI in patients with high-grade gliomas treated with bevacizumab and chemotherapy. Neurology 2006;66:1258-1260 (Pubitemid 43739717)
55. Norden AD, Young GS, Setayesh K, et al. Bevacizumab for recurrent malignant gliomas: efficacy, toxicity, and patterns of recurrence. Neurology 2008;70:779-787
56. Vredenburgh J, Desjardins A, Herndon JE 2nd, et al. Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res 2007;13:1253-1259
57. Vredenburgh J, Desjardins A, Herndon JE 2nd, et al. Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol 2007;25:4722-4729
58. Macdonald DR, Cascino TL, Schold SC Jr, Cairncross JG. Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 1990;8:1277-1280
59. Wagner SA, Desjardins A, Reardon DA, et al. Update on survival from the original phase II trial of bevacizumab and irinotecan in recurrent malignant gliomas [abstract]. J Clin Oncol 2008;26:2021
60. Cloughesy TF, Prados MD, Wen PY, et al. Phase II, randomized, noncomparative 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]. J Clin Oncol 2008;26:2010b
61. Kreisl T, 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 2009;27:740-745
62. Prados MD, Lamborn K, Yung WK, et al. A phase 2 trial of irinotecan (CPT-11) in patients with recurrent malignant glioma: a North American Brain Tumor Consortium study. Neuro-oncol 2006;8:189-193 (Pubitemid 46542664)
63. Du R, Lu KV, Petritsch C, et al. HIF1alpha induces the recruitment of bone marrow-derived vascular modulatory cells to regulate tumor angiogenesis and invasion. Cancer Cell 2008;13:206-220 (Pubitemid 351318372)
64. Holash J, Maisonpierre PC, Compton D, et al. Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science 1999;284:1994-1998 (Pubitemid 29309448)
65. Rubenstein JL, Kim J, Ozawa T, et al. Anti-VEGF antibody treatment of glioblastoma prolongs survival but results in increased vascular cooption. Neoplasia 2000;2:306-314 (Pubitemid 30703463)
66. Lassman AB, Iwamoto FM, Gutin PH, Abrey LE. Patterns of relapse and prognosis after bevacizumav (BEV) failure in recurrent glioblastoma (GBM) [abstract]. J Clin Oncol 2008;26:2028
67. Pope WB, Lai A, Nghiemphu P, et al. MRI in patients with high-grade gliomas treated with bevacizumab and chemotherapy. Neurology 2006;66:1258-1260 (Pubitemid 43739717)
68. Omuro A, Delattre J-Y. What is the place of bevacizumab and irinotecan in the treatment of glioblastoma and other malignant gliomas? Editorial comment. Curr Opin Neurol 2008;21:717-719
69. Leon SP, Folkerth RD, Black PM. Microvessel density is a prognostic indicator for patients with astroglial brain tumors. Cancer 1996;77:362-372
70. Sathornsumetee S, Cao Y, Marcello JE, et al. Tumor angiogenic and hypoxic profiles predict radiographic response and survival in malignant astrocytoma patients treated with bevacizumab and irinotecan. J Clin Oncol 2008;26:271-278
71. Duda DG, Jain RK, Willet CG. Antiangiogenetics: the potential role of integrating this novel treatment modality with chemoradiation for solid cancers. J Clin Oncol 2007;25:4033-4042
72. 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;71:1372-1380
73. 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]. J Clin Oncol 2008;26:2020
74. 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;11:83-95 (Pubitemid 46075199)
75. Di Tommaso E, Frosch MP, Auluck PK, et al. Characterization of blood vessels in brain autopsies of GBM patients who received antiangiogenic treatment [abstract]. J Clin Oncol 2008;26:2009
76. Jain RK, di Tomaso E, Duda DG, et al. Angiogenesis in brain tumor. Nat Rev Neurosci 2007;8:610-622
77. Zhou Q, Guo P, Gallo JM. Impact of angiogenesis inhibition by sunitinib on tumor distribution of temozolomide. Clin Cancer Res 2008;14:1540-1549
78. Carapancea M, Alexandru O, Fetea A, et al. Growth factor receptors signaling in glioblastoma cells: therapeutic implications. J Neurooncol 2009;92:137-147
79. Idbah A, Ducrey F, Sierra Del Rio M, et al. Therapeutic application of noncytotxic molecular targeted therapy in gliomas: growth factor receptors and angiogenesis inhibitors. Oncologist 2008;13:978-992
80. Nicholas MK, Lukas RV, Jafri NF, et al. Epidermal growth factor receptor-mediated signal transduction in the development and therapy of gliomas. Clin Cancer Res 2006;12:7261-7270 (Pubitemid 46095397)
81. Ohgaki H, Dessen P, Jourde B, et al. Genetic pathways to glioblastoma: a population-based study. Cancer Res 2004;64:6892-6899 (Pubitemid 39330996)
82. Pelloski C, Ballman K, Furth A, et al. Epidermal growth factor receptor variant III status defines clinically distinct subtypes of glioblastoma. J Clin Oncol 2007;25:2288-2294 (Pubitemid 46954657)
83. Peereboom DM, Brewer C, Stevens GHJ, et al. Phase II trial of erlotinib with temozolomide and concurrent radiation therapy post-operatively in patients with newly diagnosed glioblastoma multiforme. Neuro-oncol 2005;6:379 TA-41 (abstr.)
84. Prados MD, Lamborn KR, Chang S, et al. Phase I study of erlotinib HCI alone and combined with temozolomide in patients with stable or recurrent malignant glioma. Neuro-oncol 2006;8:67-78 (Pubitemid 43154453)
85. Mellinghoff IK, Wang MY, Vivanco I, et al. Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors. N Engl J Med 2005;353:2012-2024 (Pubitemid 41609094)
86. Haas-Kogan DA, Prados MD, Tihan T, et al. Epidermal growth factor receptor, protein kinase B/Akt, and glioma response to erlotinib. J Natl Cancer Inst 2005;97:880-887 (Pubitemid 41417939)
87. Rich JN, Reardon DA, Peery T, et al. Phase II trial of gefitinib in recurrent glioblastoma. J Clin Oncol 2004;22:133-142 (Pubitemid 41095125)
88. 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 glioblaastoma multiforme: North Central Cancer Treatment Group Study N0177. J Clin Oncol 2008;26:5603-5609
89. Franceschini E, Cavallo G, Lonardi S, et al. Gefitinib in patients with progressive high-grade gliomas: a multicentre phase II study by Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO). Br J Cancer 2007;96:1047-1051 (Pubitemid 46608313)
90. Doherty L, Gigas DC, Cesari S, et al. Pilot study of the combination of EGFR and mTOR inhibitors in recurrent malignant gliomas. Neurology 2006;67:156-158 (Pubitemid 44305484)
91. Reardon DA, Quinn JA, Vredenburgh JJ, et al. Phase I trial of gefitinib plus sirolimus in adults with recurrent malignant glioma. Clin Cancer Res 2006;12:860-868
92. Prados M, Chang S, Butowski C, 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 2009;27:579-584
93. Westphal M, Hilt DC, Bortey E, et al. A phase III trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. Neuro-oncol 2003;5:79-88 (Pubitemid 36422560)
94. Westphal M, Ram Z, Riddle V, et al. Gliadel wafer in initial surgery for malignant glioma: long-term follow-up of a multicenter controlled trial. Acta Neurochir (Wien) 2006;148:269-275 (Pubitemid 43341024)
95. Limentani SA, Asher A, Heafner M, et al. A phase I trial of surgery, Gliadel wafer implantation, and immediate postoperative carboplatin in combination with radiation therapy for primary anaplastic astrocytoma or glioblastoma multiforme. J Neurooncol 2005;72:241-244 (Pubitemid 40867407)
96. Brandes AA, Ermani M, Turazzi S, et al. Procarbazine and high-dose tamoxifen as a second- line regimen in recurrent high-grade gliomas: a phase ii study. J Clin Oncol 1999;17:645-650 (Pubitemid 29075253)
97. Couldwell WT, Hinton DR, Surnock AA, et al. Treatment of recurrent malignant gliomas with chronic oral high-dose tamoxifen. Clin Cancer Res 1996;2:619-622 (Pubitemid 26133465)
98. Chen TC, Su S, Fry D, Liebes L. Combination therapy with irinotecan and protein kinase C inhibitors in malignant glioma. Cancer 2003;97(9 Suppl):2363-2373 (Pubitemid 36444047)
99. Spence AM, Peterson RA, Scharnhorst JD, et al. Phase II study of concurrent continous temozolomide (TMZ) and tamoxifen (TMX) for recurrent malignant astrocytic gliomas. J Neurooncol 2004;70:91-95
100. Gupta V, Su YS, Wang W, et al. Enhancement of glioblastoma cell killing by combination treatment with temozolomide and tamoxifen or hypericin. Neurosurg Focus 2006;20(4):E20
101. Muanza T, Shenouda G, Souhami L, et al. High dose tamoxifen and radiotherapy in patients with glioblastoma multiforme: a phase IB study. Can J Neurol Sci 2000;27:302-306
102. Robins HI, Won M, Seiferheld WF, et al. Phase 2 trial of radiation plus high-dose tamoxifen for glioblastoma multiforme: RTOG protocol BR-0021. Neuro-oncol 2006;8:47-52 (Pubitemid 43154450)
103. Wick W, Wick A, Schulz JB, et al. Prevention of irradiation-induced glioma cell invasion by temozolomide involves caspase 3 activity and cleavage of focal adhesion kinase. Cancer Res 2002;62:1915-1919 (Pubitemid 34408522)
104. 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. ASCO Annual Meeting Proceedings Part I 2007 [abstract 2000]. J Clin Oncol 2007;25(Suppl):75s
105. Tuettenberg J, Grobholz R, Korn T, et al. Continous low-dose chemotherapy plus inhibition of cyclooxygenase-2 as an antiangiogenic therapy of glioblastoma multiforme. J Cancer Res Clin Oncol 2005;131:31-40 (Pubitemid 40064455)
106. Reardon DA, Quinn JA, Vredenburgh JA, et al. Phase II Trial of irinotecan plus celecoxib in adults with recurrent malignant glioma. Cancer 2005;103:329-338 (Pubitemid 40129293)
107. Soffietti R, Leoncini B, Rudà R. New developments in the treatment of malignant gliomas. Expert Rev Neurother 2007;7:1313-1325 (Pubitemid 350012721)
108. Yung WKA, Prados MD, Yaya-Tur R, et al. Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Temodar Brain Tumor Group. J Clin Oncol 1999;17:2762-2771 (Pubitemid 29415233)
109. Cairncross JG, Ueki K, Zlatescu MC, et al. Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Natl Cancer Inst 1998;90:1473-1479 (Pubitemid 28482012)
110. van den Bent MJ, Taphoorn MJ, Brandes AA, et al. Phase II study of first-line chemotherapy with temozolomide in recurrent oligodendroglial tumors: European Organization for Research and Treatment of Cancer Brain Tumor Group Study 26971. J Clin Oncol 2003;21:2525-2528 (Pubitemid 46606334)
111. Soffietti R. Chemotherapy of anaplastic oligodendroglial tumours. Expert Opin Pharmacother 2004;5:295-306
112. Triebels VH, Taphoorn MJ, Brandes AA, et al. Salvage PCV chemotherapy for temozolomide-resistant oligodendrogliomas. Neurology 2004;63:904-906 (Pubitemid 39297657)
113. Cairncross G, Seiferheld W, Shaw E, et al. Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402. J Clin Oncol 2006;24:2707-2714 (Pubitemid 46630566)
114. van den Bent MJ, Carpentier AF, Brandes AA, et al. Adjuvant procarbazine, lomustine, and vincristine improves progression-free survival but not overall survival in newly diagnosed anaplastic oligodendrogliomas: a randomized European Organization for Research and Treatment of Cancer Phase III trial. J Clin Oncol 2006;24:2715-2722
115. Abrey LE, Louis DN, Paleologos N, et al. Survey of treatment recommendations for anaplastic oligodendroglioma. Neuro-oncol 2007;9:314-318 (Pubitemid 47169664)