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Glioblastoma multiforme. Glioblastoma multiforme Histological Classification. Astrocytic Tumors : Meningeal Tumors Astrocytoma WHO I-IV Meningeoma Pleomorphic Xantho-astrocytoma Haemangiopericytoma Subependymal Giant-cell astrocytoma Melanocytic Tumors
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Glioblastoma multiformeHistological Classification Astrocytic Tumors: Meningeal Tumors Astrocytoma WHO I-IV Meningeoma Pleomorphic Xantho-astrocytoma Haemangiopericytoma Subependymal Giant-cell astrocytoma Melanocytic Tumors Oligodendroglial Tumors Haemangioblastoma Mixed Gliomas Ependymal TumorsPrimary CNS Lymphoma Plexus choroideus Tumors Neuronal and mixed, neuronal-glial TumorsGerm Cell Tumors Gangliocytoma Germinoma Ganglioglioma Embryonal Carcinoma Pinealoocytoma Endodermal Sinustumor Embryonal Tumors Chorioncarcinoma MedulloblastomaHypophyseal Adenoma Primitive neuroectodermal Tumors (PNET)Craniopharyngioma Simplified according to WHO Classification
Glioblastoma multiformeSymptoms Symptoms Patients (%) Lisa de Angelis, NEJM 2001
Glioblastoma multiforme Chemotherapeutic regimens I • CCNU 80-120 mg/m2 per os q 42 • Fotemustine 100 mg/m2 • Dacarbacine 200 mg/m2 • Carboplatin 150 mg/m2 d 1-3 • Etoposid 100 mg/m2 d1-3 q 21 q 21
Glioblastoma multiformeChemotherapeutic regimens II • Cisplatin 20mg/m2, day 1 • CCNU 80 mg/m2, day 1 • Vincristin 2mg, day 8 + 21 • Procarbacine 60 mg/m2, day 8 -21, q 42
Glioblastoma multiformeNeurosurgical procedures Group A B C n = 100 93 100 „complete“ resection 78 32 28 partial resection 22 21 46 stereotactic biopsy 0 40 21
Glioblastoma multiformePostsurgical treatment Group A B C n = 100 93 100 Radiotherapy 22 58 95 Chemotherapy 6 30 98
Glioblastoma multiformeOutcome of patients Group A B C n 100 93 100 early death 19 24 5 (within 10 weeks after diagnosis) survival > 1 year 24 12 33 progression free n.d. n.d. 28
Glioblastoma multiformeTherapy at relapse Group A B C surgical resection 38 5 8 Chemotherapy 2nd line0 2 12
Glioblastoma multiformeChemotherapeutic regimens Group A B C Polychemotherapy 6 19 0 (German Austrian Study) Carboplatin/Etoposid 0 4 10 CCNU 0 7 66 Fotemustine/Dacarbacine 0 0 22
Glioblastoma multiformeAdjuvant Chemotherapy • Chemotherapy is feasible • Outpatient treatment is safe • Side effects are manageable • Results in long-term survivors • Benefit also for older patients • Benefit for patients with inoperable tumors
Glioblastoma multiformeChemotherapy • Fotemustine 100 mg /m2 • Dacarbacine 200 mg /m2 intravenous q 21 days x8
Glioblastoma multiformePCVChemotherapy of anaplastic oligodendroglioma • CCNU 110 mg /m2, day 1 • Vincristin 2 mg, day 8 + 29 • Procarbacin 60 mg /m2, day 8-21
Glioblastoma multiformeResponse to PCV inrecurrent oligodendroglioma
Glioblastoma multiformeChemotherapy • CCNU 100 mg /m2 orally, q 6-8 weeks for one year
Glioblastoma multiformeToxicity of chemotherapeutic regimens
Glioblastoma multiformeInhibition of angiogenensis:An attractive therapeutic approach in malignant tumors • highly tumor-selective • overexpression of VEGF in tumors as repeatedly demonstrated in GBM, especially near necrotic areas
Glioblastoma multiformeThalidomidein recurrent malignant glioma Thalidomide 800 mg /day - 1200 mg/day Patients: n = 39 recurrent glioblastoma multiforme 25 recurrent anaplastic astrocytoma 12 recurrent anaplastic mixed glioma 2 Fine HA et al, JCO 18:708-715, 2000
Glioblastoma multiformeThalidomidein recurrent malignant glioma TTP median 10 weeks OAS median 28 weeks radiographic response partial 2/39 stable 12/39 progressive 20/39 Fine HA et al, JCO 18:708-715, 2000