First experiences with low-dose anti-angiogenic treatment in gliomatosis cerebri with signs of angiogenic activity.
BACKGROUND
Gliomatosis cerebri is a rare primary cerebral tumour entity characterized by diffuse infiltrative growth patterns representing a WHO grade III malignancy. The prognosis is dismal and therapeutical options are still controversial. In contrast to other high-grade gliomas, angiogenesis is thought to be absent in gliomatosis cerebri.


METHODS
Despite this assumption, histopathological analyses of samples of six patients with gliomatosis cerebri were performed and surprisingly there was angiogenic activity with expression of vascular endothelial growth factor and cyclooxygenase 2. It was therefore decided to administer continuous low-dose chemotherapy with temozolomide and celecoxib for antiangiogenic treatment in the four patients that were in good clinical condition following external radiotherapy.


RESULTS
In all patients, treatment was well tolerated and MRI follow-up showed no tumour progression for at least six months. One patient died due to pulmonary embolism 9 months after diagnosis; another patient survived 15 months after diagnosis with progressive disease in the last follow-up MRI before death. Two other patients at the present time are still in a stable clinical condition without signs of tumour progression in MRI (12 and 18 months).


CONCLUSIONS
From our initial experience in a small number of patients with gliomatosis cerebri with signs of angiogenic activity, we conclude that low-dose chemotherapy might provide a promising approach for treatment of these patients and that overexpression of angiogenic factors such as VEGF or COX-2 seems to be more frequent than hitherto reported.
Seiz
Marcel
M
Department of Neurosurgery, Ruprecht-Karls University Heidelberg, Medical Faculty Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. marcel.seiz@umm.de
Kohlhof
Patricia
P
Brockmann
Marc Alexander
MA
Neumaier-Probst
Eva
E
Hermes
Petra
P
VON Deimling
Andreas
A
Vajkoczy
Peter
P
Schmieder
Kirsten
K
Tuettenberg
Jochen
J
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068579:Celecoxib; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018302:Neoplasms, Neuroepithelial / Q000098:blood supply* / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D011379:Prognosis; D011720:Pyrazoles / Q000008:administration & dosage; D013449:Sulfonamides / Q000008:administration & dosage; D015996:Survival Rate; D000077204:Temozolomide; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D011720:Pyrazoles; D013449:Sulfonamides; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D003606:Dacarbazine; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000068579:Celecoxib; D000077204:Temozolomide