Pediatric patients with refractory central nervous system tumors: Experiences of a clinical trial combining bevacizumab and temsirolimus

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 welltolerated and resulted in stable disease of at least four months/partial response in three out of six pediatric patients with chemorefractory CNS tumors.