BACKGROUND: Pre-clinical findings suggest that combination treatment with 
bevacizumab and temsirolimus could be effective against malignant pediatric 
central nervous system (CNS) tumors.
PATIENTS AND METHODS: Six pediatric patients were treated as part of a phase I 
trial with intravenous temsirolimus 25 mg on days 1, 8, 15, and bevacizumab at 
5, 10, or 15 mg/kg on day 1 of each 21-day cycle until disease progression or 
patient withdrawal.
RESULTS: The median patient age was six years (range=3-14 years). The primary 
diagnoses were glioblastoma multiforme (n=2), medullobalstoma (n=2), pontine 
glioma (n=1) and ependymoma (n=1). All patients had disease refractory to 
standard-of-care (2-3 prior systemic therapies). Grade 3 toxicities possibly 
related to drugs used occurred in two patients: anorexia, nausea, and weight 
loss in one, and thrombocytopenia and alanine aminotransferase elevation in 
another. One patient with glioblastoma multiforme achieved a partial response 
(51% regression) and two patients (with medulloblastoma and pontine glioma) had 
stable disease for four months or more (20 and 47 weeks, respectively). One 
other patient (with glioblastoma multiforme) showed 18% tumor regression 
(duration=12 weeks).
CONCLUSION: The combination of bevacizumab with temsirolimus was well-tolerated 
and resulted in stable disease of at least four months/partial response in three 
out of six pediatric patients with chemorefractory CNS tumors.