Sustained Survival Benefit in Recurrent Medulloblastoma by a Metronomic Antiangiogenic Regimen

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Abstract
Medulloblastoma, an aggressive embryonal tumor arising in the cerebellum or, less frequently, in the dorsal brain stem, is one of the most common malignant central nervous system tumors in children.1 Four clinically relevant molecular subgroups—WNT (wingless-related integration site), SHH (sonic hedgehog signaling molecule), group 3, and group 4—are known2 and have been differentiated into additional subtypes.3-5 Unfortunately, identification of these subgroups has not yet translated into more effective targeted therapies. Surgery, craniospinal irradiation, and multiagent chemotherapy remain the standard up-front treatment approach for most patients. Although this treatment is highly effective for most patients, approximately 30% of patients will experience relapse of their disease, often metastatic at the time of relapse, and most will eventually die of their disease.6-12 A widely used treatment strategy for recurrent medulloblastoma is the combination of temozolomide and irinotecan,13 which was recently augmented with bevacizumab.14 This treatment regimen was well tolerated and had an acceptable response rate but failed to lead to sustained responses in patients who had previously received irradiation.

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