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Die Onkologie

Erschienen in:

01.01.2011 | Leitthema

Chemotherapie bei Gliomen

verfasst von: Prof. Dr. W. Wick, F. Winkler, M. Platten

Erschienen in: Die Onkologie | Ausgabe 1/2011

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Zusammenfassung

Aktuelle Strategien der Primärtherapie von Gliomen zielen auf eine Ergänzung der kombinierten Radiochemotherapie mit Temozolomid um zumeist zielgerichtete Therapeutika. Alternativ werden bei Patienten, bei denen aufgrund der Aktivität des DNA-Reparaturenzyms O6-Methyl-Guanyl-Methyl-Transferase (MGMT) ein geringeres Ansprechen auf Alkylanzien wie Temozolomid postuliert wird, alkylanzienfreie Kombinationstherapien mit der Radiotherapie getestet. Zielgerichtete Therapeutika wie z. B. Cilengitid, Enzastaurin, Temsirolimus, Cediranib, Epidermal-Growth-Factor-Receptor- (EGFR-)Inhibitoren oder der monoklonale Vascular-Endothelial-Growth-Factor- (VEGF-)Antikörper Bevacizumab werden als Monotherapie im Rezidiv und in den genannten Kombinationen in der Primärtherapie untersucht. Nachdem aus den bisherigen Therapiestudien abgeleitet werden kann, dass diese zielgerichteten Therapien, wenn überhaupt, jeweils nur für einen Teil der Patienten wirksam sind, wird die nächste relevante Entwicklung der Therapie von Gliomen durch die Bestimmung prädiktiver Signaturen erwartet.

Stupp R, Mason WP, Bent MJ van den et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996CrossRefPubMed

Wen PY, Kesari S (2008) Malignant gliomas in adults. N Engl J Med 359:492–507CrossRefPubMed

Wick A, Pascher C, Wick W et al (2009) Rechallenge with temozolomide in patients with recurrent gliomas. J Neurol 256:734–741CrossRefPubMed

Perry JR, Belanger K, Mason WP et al (2010) Phase II trial of continuous dose-intense temozolomide in recurrent malignant glioma: RESCUE study. J Clin Oncol 28:2051–2057CrossRefPubMed

Wick W, Engel C, Combs SE et al (2010) NOA-08 randomized phase III trial of 1-week-on/1-week-off temozolomide versus involved field radiotherapy in elderly (older than age 65) patients with newly diagnosed anaplastic astrocytoma or glioblastoma (Methusalem). J Clin Oncol 28:7 s (suppl; abstr. LBA2001)CrossRef

Weller M, Tabatabai G, Reifenberger G et al (2010) Dose-intensified Rechallenge with Temozolomide, One Week on / One Week Off versus 3 Weeks on / One Week Off in Patients with Progressive or Recurrent Glioblastoma. J Clin Oncol 28:7 s (suppl; abstr.)CrossRef

Van den Bent MJ, Carpentier AF, Brandes AA et al (2006) Adjuvant procarbazine, lomustine, and vincristine improves progression-free survival but not overall survival in newly diagnosed anaplastic oligodendrogliomas and oligoastrocytomas: a randomized European Organisation for Research and Treatment of Cancer phase III trial. J Clin Oncol 24:2715–2722CrossRef

Cairncross G, Berkey B, Shaw E et al (2006) 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 24:2707–2714CrossRefPubMed

Wick W, Hartmann C, Engel C et al for the Neurooncology Working Group (NOA) of the German Cancer Society (2009) NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide. J Clin Oncol 27:5874–5880CrossRefPubMed

10.

Keime-Guibert F, Chinot O, Taillandier L et al (2007) Radiotherapy for glioblastoma in the elderly. N Engl J Med 356:1527–1535CrossRefPubMed

11.

Wick W, Steinbach JP, Küker WM et al (2004) One week on/one week off: a novel active regimen of temozolomide for recurrent glioblastoma. Neurology 62:2113–2115PubMed

12.

Wick A, Felsberg J, Steinbach JP et al (2007) Efficacy and tolerability of Temozolomide in an one week on/one week off regimen in patients with recurrent glioma. J Clin Oncol 25:3357–3361CrossRefPubMed

13.

Roa W, Brasher PM, Bauman G et al (2004) Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial. J Clin Oncol 22:1583–1588CrossRefPubMed

14.

Malmstrom A, Grønberg BH, Stupp R et al (2010) Glioblastoma (GBM) in elderly patients: A randomized phase III trial comparing survival in patients treated with 6-week radiotherapy (RT) versus hypofractionated RT over 2 weeks versus temozolomide single-agent chemotherapy (TMZ). J Clin Oncol 28:7 s (suppl; abstr. LBA2002)CrossRef

15.

Stupp R, Hegi ME, Mason WP et al (2009) 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 10:459–466CrossRefPubMed

16.

Hegi ME, Diserens A-C, Gorlia T et al (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003CrossRefPubMed

17.

Chi AS, Sorensen AG, Jain RK et al (2009) Angiogenesis as a therapeutic target in malignant gliomas. Oncologist 14:621–636CrossRefPubMed

18.

Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285:1182–1186CrossRefPubMed

19.

Ma J, Pulfer S, Li S et al (2001) Pharmacodynamic-mediated reduction of temozolomide tumor concentrations by the angiogenesis inhibitor TNP-470. Cancer Res 61:5491–5498PubMed

20.

Friedmann HS, Prados MD, Wen PY et al (2009) Bevazicumab alone and in combination with Irinotecan in recurrent glioblastoma. J Clin Oncol 27:4733–4740CrossRef

21.

Wick A, Dorner N, Hofer S et al. Bevacizumab does not increase the risk of remote relapse in malignant glioma. Ann Neurol (in press)

22.

The Cancer Genome Atlas Research Network (2008) Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455:1061–1068CrossRef

23.

Hartmann C, Hentschel B, Wick W et al (2010) Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: implications for classification of gliomas. Acta Neuropathol

24.

Parsons DW, Jones S, Zhang X et al (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321:1807–1812CrossRefPubMed

25.

Kil IS, Kim SY, Lee SJ et al (2007) Small interfering RNA-mediated silencing of mitochondrial NADP+-dependent isocitrate dehydrogenase enhances the sensitivity of HeLa cells toward tumor necrosis factor-alpha and anticancer drugs. Free Radic Biol Med 43:1197–1207CrossRefPubMed

26.

Weller M, Felsberg J, Hartmann C et al (2009) Molecular predictors of progression-free and overall survival in patients with newly diagnosed glioblastoma: a prospective translational study of the german glioma network. J Clin Oncol 27:5743–5750CrossRefPubMed

27.

Dang L, White DW, Gross S et al (2009) Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462:739–744CrossRefPubMed

28.

Du J, Bernasconi P, Clauser KR et al (2009) Bead-based profiling of tyrosine kinase phosphorylation identifies SRC as a potential target for glioblastoma therapy. Nat Biotechnol 27:77–83CrossRefPubMed

29.

Mitra SK, Schlaepfer DD (2006) Integrin-regulated FAK-Src signaling in normal and cancer cells. Curr Opin Cell Biol 18:516–523CrossRefPubMed

30.

Lu KV, Zhu S, Cvrljevic A et al (2009) Fyn and SRC are effectors of oncogenic epidermal growth factor receptor signaling in glioblastoma patients. Cancer Res 69:6889–6898CrossRefPubMed

31.

Combs SE, Hartmann C, Welzel J et al (2009) Influence of expression of EGFR and PTEN on outcome in patients with primary glioblastoma treated with standard radiochemotherapy and cetuximab: Interim analysis from the GERT-Protocol. J Clin Oncol 27(Suppl 15 s):99 s (abstract 2050)

32.

Stupp R, Hegi ME, Neyns B et al (2010) Phase I/IIa study of cilengitide and temozolomide with concomitant radiotherapy followed by cilengitide and temozolomide maintenance therapy in patients with newly diagnosed glioblastoma. J Clin Oncol 28:2712–2718CrossRefPubMed

33.

Brown PD, Krishnan S, Sarkaria JN et al (2008) 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 26:5603–5609CrossRefPubMed

34.

Prados MD, Chang SM, Butowski N et al (2009) Phase II study of erlotinib plus temozolomide during and after radiation therapy in patients with newly diagnosed glioblastoma multiforme or gliosarcoma. J Clin Oncol 27:579–584CrossRefPubMed

35.

Hainsworth JD, Ervin T, Friedman E et al (2010) Concurrent radiotherapy and temozolomide followed by temozolomide and sorafenib in the first-line treatment of patients with glioblastoma multiforme. Cancer 116:3663–3669CrossRefPubMed

36.

Grossman SA, Ye X, Chamberlain M et al (2009) Talampanel with standard radiation and temozolomide in patients with newly diagnosed glioblastoma: a multicenter phase II trial. J Clin Oncol 27:4155–4161CrossRefPubMed

37.

Reardon D, Cloughesy T, Raizer J et al (2008) Phase II study of AMG 102, a fully human neutralizing antibody against hepatocyte growth factor/scatter factor, in patients with recurrent glioblastoma multiforme. J Clin Oncol 26(Suppl 15 s):101 s (abstract 2051)CrossRef

38.

Reardon DA, Fink KL, Mikkelsen T et al (2008) Randomized phase II study of cilengitide, an integrin-targeting arginine-glycine-aspartic acid peptide, in recurrent glioblastoma multiforme. J Clin Oncol 26:5610–5617CrossRefPubMed

39.

Kreisl TN, Kotliarova S, Butman JA et al (2010) A phase I/II trial of enzastaurin in patients with recurrent high-grade gliomas. Neuro Oncol 12:181–189PubMed

40.

Wick W, Puduvalli VK, Chamberlain MC et al (2010) Phase III study of enzastaurin compared with lomustine in the treatment of recurrent intracranial glioblastoma. J Clin Oncol 28:1168–1174CrossRefPubMed

41.

Chang SM, Kuhn J, Lamborn KR et al (2009) Phase I/II study of erlotinib and temsirolimus for patients with recurrent malignant gliomas (MG) (NABTC 04-02). J Clin Oncol 27(Suppl 15 s):88 s (abstract 2004)

42.

Bent MJ van den, Brandes AA, Rampling R et al (2009) Randomized phase II trial of erlotinib versus temozolomide or carmustine in recurrent glioblastoma: EORTC brain tumor group study 26034. J Clin Oncol 27:1268–1274CrossRefPubMed

43.

Sathornsumetee S, Desjardins A, Vredenburgh JJ et al (2009) Phase II study of bevacizumab plus erlotinib for recurrent malignant gliomas. J Clin Oncol 27(Suppl 15 s):98 s (abstract 2045)

44.

Groot JF de, Gilbert MR, Aldape K et al (2008) Phase II study of carboplatin and erlotinib (Tarceva, OSI-774) in patients with recurrent glioblastoma. J Neurooncol 90:89–97CrossRefPubMed

45.

Reardon DA, Desjardins A, Vredenburgh JJ et al (2010) Phase 2 trial of erlotinib plus sirolimus in adults with recurrent glioblastoma. J Neurooncol 96:219–230CrossRefPubMed

46.

Franceschi E, Cavallo G, Lonardi S et al (2007) Gefitinib in patients with progressive high-grade gliomas: a multicentre phase II study by Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO). Br J Cancer 96:1047–1051CrossRefPubMed

47.

Reardon DA, Egorin MJ, Desjardins A et al (2009) Phase I pharmacokinetic study of the vascular endothelial growth factor receptor tyrosine kinase inhibitor vatalanib (PTK787) plus imatinib and hydroxyurea for malignant glioma. Cancer 115:2188–2198CrossRefPubMed

48.

Desjardins A, Quinn JA, Vredenburgh JJ et al (2007) Phase II study of imatinib mesylate and hydroxyurea for recurrent grade III malignant gliomas. J Neurooncol 83:53–60CrossRefPubMed

49.

Wen PY, Yung WK, Lamborn KR et al (2006) Phase I/II study of imatinib mesylate for recurrent malignant gliomas: North American Brain Tumor Consortium Study 99-08. Clin Cancer Res 12:4899–4907CrossRefPubMed

50.

Raymond E, Brandes AA, Dittrich C et al (2008) Phase II study of imatinib in patients with recurrent gliomas of various histologies: a European Organisation for Research and Treatment of Cancer Brain Tumor Group Study. J Clin Oncol 26:4659–4665CrossRefPubMed

51.

Reardon DA, Dresemann G, Taillibert S et al (2009) Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma. Br J Cancer 101:1995–2004CrossRefPubMed

52.

Dresemann G, Weller M, Rosenthal MA et al (2010) Imatinib in combination with hydroxyurea versus hydroxyurea alone as oral therapy in patients with progressive pretreated glioblastoma resistant to standard dose temozolomide. J Neurooncol 96:393–402CrossRefPubMed

53.

Thiessen B, Stewart C, Tsao M et al (2009) A phase I/II trial of GW572016 (lapatinib) in recurrent glioblastoma multiforme: clinical outcomes, pharmacokinetics and molecular correlation. Cancer Chemother Pharmacol Epub June 5

54.

Prados MD, Gilbert M, Kuhn J et al (2009) Phase I/II study of sorafenib and erlotinib for patients with recurrent glioblastoma (GBM) (NABTC 05-02). J Clin Oncol 27(Suppl 15 s):88 s (abstract 2005)

55.

Iwamoto FM, Kreisl TN, Kim L et al (2010) Phase 2 trial of talampanel, a glutamate receptor inhibitor, for adults with recurrent malignant gliomas. Cancer 116:1776–1782CrossRefPubMed

56.

Mellinghoff IK, Wang MY, Vivanco I et al (2005) Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors. N Engl J Med 353:2012–2024CrossRefPubMed

57.

Steinbach JP, Klumpp A, Wolburg H et al (2004) Inhibition of epidermal growth factor receptor signaling protects human malignant glioma cells from hypoxia-induced cell death. Cancer Res 64:1575–1578CrossRefPubMed

58.

Opel D, Westhoff MA, Bender A et al (2008) Phosphatidylinositol 3-kinase inhibition broadly sensitizes glioblastoma cells to death receptor- and drug-induced apoptosis. Cancer Res 68:6271–6280CrossRefPubMed

59.

Graff JR, McNulty AM, Hanna KR et al (2005) The protein kinase Cbeta-selective inhibitor, Enzastaurin (LY317615.HCl), suppresses signaling through the AKT pathway, induces apoptosis, and suppresses growth of human colon cancer and glioblastoma xenografts. Cancer Res 65:7462–7469CrossRefPubMed

60.

Tabatabai G, Frank B, Wick A et al (2007) Synergistic antiglioma activity of radiotherapy and enzastaurin. Ann Neurol 61:153–161CrossRefPubMed

61.

Brave M, Goodman V, Kaminskas E et al (2008) Sprycel for chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia resistant to or intolerant of imatinib mesylate. Clin Cancer Res 14:352–359CrossRefPubMed

62.

Lombardo LJ, Lee FY, Chen P et al (2004) Discovery of N-(2-chloro-6-methyl-phenyl)-2-(6-(4-(2-hydroxyethyl)-piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays. J Med Chem 47:6658–6661CrossRefPubMed

63.

Kleihues P, Ohgaki H (1999) Primary and secondary glioblastomas: from concept to clinical diagnosis. Neuro Oncol 1:44–51PubMed

64.

Wilhelm SM, Adnane L, Newell P et al (2008) Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling. Mol Cancer Ther 7:3129–3140CrossRefPubMed

65.

Holdhoff M, Kreuzer KA, Appelt C et al (2005) Imatinib mesylate radiosensitizes human glioblastoma cells through inhibition of platelet-derived growth factor receptor. Blood Cells Mol Dis 34:181–185CrossRefPubMed

66.

Kamoun WS, Ley CD, Farrar CT et al (2009) 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 27:2542–2552CrossRefPubMed

67.

Batchelor TT, Sorensen AG, Tomaso E di et al (2007) AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell 11:83–95CrossRefPubMed

68.

Batchelor T, Mulholland P, Neyns B et al (2010) A phase III randomized study comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, with lomustine alone in recurrent glioblastoma patients. Ann Oncol 21(Suppl 8):viii4 (LBA7)

69.

Mikkelsen T, Brodie C, Finniss S et al (2009) Radiation sensitization of glioblastoma by cilengitide has unanticipated schedule-dependency. Int J Cancer 124:2719–2727CrossRefPubMed

70.

Maurer GD, Tritschler I, Adams B et al (2009) Cilengitide modulates attachment and viability of human glioma cells, but not sensitivity to irradiation or temozolomide in vitro. Neuro Oncol 11:747–756CrossRefPubMed

71.

Kong DS, Song SY, Kim DH et al (2009) Prognostic significance of c-Met expression in glioblastomas. Cancer 115:140–148CrossRefPubMed

72.

Yamazaki S, Skaptason J, Romero D et al (2008) Pharmacokinetic-pharmacodynamic modeling of biomarker response and tumor growth inhibition to an orally available cMet kinase inhibitor in human tumor xenograft mouse models. Drug Metab Dispos 36:1267–1274CrossRefPubMed

73.

Roth W, Isenmann S, Nakamura M et al (2001) The soluble decoy receptor-3 is expressed by malignant gliomas and suppresses CD95 ligand-induced apoptosis and chemotaxis. Cancer Res 61:2759–2765PubMed

74.

Kleber S, Sancho-Martinez I, Wiestler B et al (2008) Yes and PI3 K bind CD95 to signal invasion of glioblastoma. Cancer Cell 13:235–248CrossRefPubMed

Titel: Chemotherapie bei Gliomen
verfasst von: Prof. Dr. W. Wick
F. Winkler
M. Platten
Publikationsdatum: 01.01.2011
Verlag: Springer-Verlag
Erschienen in: Die Onkologie / Ausgabe 1/2011
Print ISSN: 2731-7226
Elektronische ISSN: 2731-7234
DOI: https://doi.org/10.1007/s00761-010-1962-z

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