Onkologische Welt 2011; 02(02): 89-93
DOI: 10.1055/s-0038-1631233
Neuro-Onkologie
Schattauer GmbH

Neuentwicklungen in der Neuro-Onkologie

Update in neurooncology
U. Schlegel
1   Universitätsklinik für Neurologie, Knappschaftskrankenhaus Bochum
› Institutsangaben
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Publikationsverlauf

Publikationsdatum:
02. Februar 2018 (online)

Zusammenfassung

Die Standardtherapie des Glioblastoms im Erwachsenenalter besteht aus operativer Resektion, Bestrahlung der erweiterten Tumorregion begleitet von einer kontinuierlichen Temozolomidtherapie, gefolgt von sechs Zyklen einer adjuvanten Temozolomidtherapie. Therapiestudien mit dem Ziel, diese Standardtherapie zu verbessern, werden mit dem Integrinantagonisten Cilengitide, mit Tyrosinkinaseinhibitoren, mit dem PKC-β-Hemmer Enzastaurin, mit Neoangiogenesehemmern und mit anderen Substanzen durchgeführt. In der Rezidivtherapie werden unter anderem intensivierte Chemotherapieprotokolle und der Neoangiogenesehemmer Bevacizumab eingesetzt. In der Primärtherapie und im Rezidiv enttäuscht haben targeted therapies mit „small molecules“. Für die anaplastischen Gliome, WHO Grad III, hat die NOA-04-Studie einen neuen Therapiestandard definiert. Obwohl es keine „Standardtherapie“ der primären ZNS-Lymphome (PZNSL) gibt, soll primär eine Methotrexat-(MTX)-basierte systemische Chemotherapie eingesetzt werden. Eine primäre Strahlentherapie der PZNSL allein wird nicht empfohlen und ihr Einsatz als konsolidierende Maßnahme nach einer MTX-basierten Chemotherapie bringt nach neuesten Daten keinen Überlebensvorteil. Die Therapie der Wahl bei PZNSL besteht in einer MTX-basierten Polychemotherapie. Bei Patienten unter 60 werden damit kurative Therapieansätze verfolgt. In Deutschland gibt es gut organisierte Studiengruppen. Die Patienten sollten möglichst alle innerhalb dieser Studien behandelt werden.

Summary

The standard of care in adult glioblastoma is tumour resection followed by concomitant radio-/chemotherapy with temozolomide and 6 cycles of adjuvant temozolomide. To improve this standard, clinical trials have evaluated/evaluate efficacy and toxicity of cilengitide, an integrin antagonist, inhibitors of tyrosine kinases, of PKC-β and of neo-angiogenesis among other substances. In the recurrent situation intensified chemotherapy regimens are applied as well as bevacizumab, an antibody to the vascular endothelial growth factor. For recurrent glioblastoma, results with small molecules have been disappointing. For anaplastic glioma, WHO grade III, results of the NOA04-trial, have established a new standard. There is no “standard” therapy for primary CNS lymphoma. Methotrexate (MTX)-based chemotherapy should be considered first. A primary radiotherapy is not recommended, its usefulness as “consolidating” therapy after chemo could not be shown by a large prospective randomized trial. Today’s therapy of choice is a MTX-based polychemotherapy. In patients at age 60 years or younger this therapy is given in a curative approach. In Germany there are well-organized study groups. If possible, all patients should be treated within clinical trials.

 
  • Literatur

  • 1 Batchelor TT, Duda DG, di Tomaso E. et al. Phase II Study of cediranib, an oral pan-vascular endothelial growth factor Rreceptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. J Clin Oncol 2010; 28: 2817-2823.
  • 2 Blumenthal DT, Won M, Mehta MP. et al. Short delay in initiation of radiotherapy may not affect outcome of patients with glioblastoma: a secondary analysis from the radiation therapy oncology group database. J Clin Oncol 2009; 27: 733-739.
  • 3 Correa DD, Rocco-Donovan M. et al. Prospective cognitive follow-up in primary CNS lymphoma patients treated with chemotherapy and reduced-dose radiotherapy. J Neurooncol 2009; 91: 315-321.
  • 4 Ferreri AJ, Reni M, Foppoli M. et al. High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate alone in patients with primary CNS lymphoma: a randomised phase 2 trial. Lancet 2009; 374: 1512-20.
  • 5 Fischer L, Martus P, Weller M, Klasen HA, Rohden B, Roth A. et al. Meningeal dissemination in primary CNS lymphoma: prospective evaluation of 282 patients. Neurology 2008; 71: 1102-1108.
  • 6 Friedman HS, Prados MD, Wen PY. et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 2009; 27: 4733-4740.
  • 7 Glas M, Happold C, Rieger J, Wiewrodt D, Bahr O, Steinbach JP. et al. Long-term survival of patients with glioblastoma treated with radiotherapy and lomustine plus temozolomide. J Clin Oncol 2009; 27: 1257-61.
  • 8 Hau P, Jachimczak P, Schlingensiepen R. et al. Inhibition of TGF-beta2 with AP 12009 in recurrent malignant gliomas: from preclinical to phase I/II studies. Oligonucleotides. 2007; 17: 201-212.
  • 9 Herrlinger U, Küker W, Uhl M. et al. NOA-03 trial of high-dose methotrexate in primary central nervous system lymphoma: final report. Ann Neurol 2005; 57: 843-7.
  • 10 Horger M, Fenchel M, Nagele T. et al. Water diffusivity: comparison of primary CNS lymphoma and astrocytic tumor infiltrating the corpus callosum. AJR Am J Roentgenol 2009; 193: 1384-1387.
  • 11 Hottinger AF, DeAngelis LM, Yahalom J, Abrey LE. Salvage whole brain radiotherapy for recurrent or refractory primary CNS lymphoma. Neurology 2007; 69: 1178-1182.
  • 12 Illerhaus G, Muller F, Feuerhake F. et al. High-dose chemotherapy and autologous stem-cell transplantation without consolidating radiotherapy as first-line treatment for primary lymphoma of the central nervous system. Haematologica 2008; 93: 147-148.
  • 13 Juergens A, Pels H, Rogowski S. et al. Long-term survival with favorable cognitive outcome after chemotherapy in primary central nervous system lymphoma. Ann Neurol 2010; 67: 182-189.
  • 14 Kaloshi G, Benouaich-Amiel A, Diakite F. et al. Temozolomide for low-grade gliomas: predictive impact of 1p/19q loss on response and outcome. Neurology 2007; 68: 1831-1836.
  • 15 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 2009; 27: 740-745.
  • 16 McCann KJ, Ashton-Key M, Smith K. et al. Primary central nervous system lymphoma: tumor-related clones exist in the blood and bone marrow with evidence for separate development. Blood 2009; 113: 4677-4680.
  • 17 McGirt MJ, Chaichana KL, Attenello FJ. et al. Extent of surgical resection is independently associated with survival in patients with hemispheric infiltrating low-grade glioms. Neurosurgery 2008; 63: 700-707.
  • 18 Montesinos-Rongen M, Brunn A, Bentink S, Basso K, Lim WK, Klapper W. et al. Gene expression profiling suggests primary central nervous system lymphomas to be derived from a late germinal center B cell. Leukemia 2008; 22: 400-405.
  • 19 Porter AB, Giannini C, Kaufmann T. et al. Primary central nervous system lymphoma can be histologically diagnosed after previous corticosteroid use: a pilot study to determine whether corticosteroids prevent the diagnosis of primary central nervous system lymphoma. Ann Neurol 2008; 63: 662-667.
  • 20 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 2009; 27: 579-584.
  • 21 Ricard D, Kaloshi G, Amiel-Benouaich A. et al. Dynamic history of low-grade gliomas before and after temozolomide treatment. Ann Neurol 2007; 61: 484-490.
  • 22 Schlegel U, Korfel A, Thiel E. et al. Primäre ZNS Lymphome. Der Onkologe. 2009: 211-221.
  • 23 Schlingensiepen KH, Schlingensiepen R, Steinbrecher A. et al. Targeted tumor therapy with the TGF-beta 2 antisense compound AP 12009. Cytokine Growth Factor Rev 2006; 17: 129-139.
  • 24 Smith JS, Chang EF, Lamborn KR. et al. Role of extent of resection in the long-term outcome of low-grade hemispheric gliomas. J Clin Oncol 2008; 26: 1338-1345.
  • 25 Stupp R, Hegi M, Neyns B. et al. Phase I/IIa trial of cilengitide and temozolomide with concomitant radiotherapy, followed by temozolomide and cilengitide maintenance therapy in patients with newly diagnosed glioblastoma. J Clin Oncol 2010; 28: 2712-2718.
  • 26 Stupp R, Hegi ME, Mason WP. 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.
  • 27 Tabatabai G, Frank B, Wick A. et al. Synergistic antiglioma activity of radiotherapy and enzastaurin. Ann Neurol 2007; 6: 153-161.
  • 28 Vredenburgh JJ, Desjardins A, Herndon JE. et al. Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol 2007; 25: 4722-4729.
  • 29 Wick A, Felsberg J, Steinbach JP. et al. Efficacy and tolerability of temozolomide in an alternating weekly regimen in patients with recurrent glioma. J Clin Oncol 2007; 25: 3357-3361.
  • 30 Wick A, Pascher C, Wick W. et al. Rechallenge with temozolomide in patients with recurrent gliomas. J Neurol 2009; 256: 734-741.
  • 31 Wick W, Hartmann C, Engel C. et al. NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol 2009; 27: 5874-5880.
  • 32 Thiel et al. Präsentation ASCO. 2010