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. PATIENTS AND 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). CONCLUSION 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.