title: Pediatric patients with refractory central nervous system tumors: experiences of a clinical trial combining bevacizumab and temsirolimus.
abstract: BACKGROUND
  Pre-clinical findings suggest that combination treatment with bevacizumab and temsirolimus could be effective against malignant pediatric central nervous system (CNS) tumors.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 1500 Holcombe Boulevard, Unit 455, Houston, TX 77030, U.S.A. spihapau@mdanderson.org.
authors.forename: Sarina A
authors.initials: SA
authors.lastname: Piha-Paul
authors.forename: Sang Joon
authors.initials: SJ
authors.lastname: Shin
authors.forename: Tribhawan
authors.initials: T
authors.lastname: Vats
authors.forename: Nandita
authors.initials: N
authors.lastname: Guha-Thakurta
authors.forename: Joann
authors.initials: J
authors.lastname: Aaron
authors.forename: Michael
authors.initials: M
authors.lastname: Rytting
authors.forename: Eugenie
authors.initials: E
authors.lastname: Kleinerman
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
mesh_terms: D000293:Adolescent; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000175:diagnosis / Q000628:therapy; D016543:Central Nervous System Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D006801:Humans; D008279:Magnetic Resonance Imaging; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D047428:Protein Kinase Inhibitors; D000068258:Bevacizumab; C401859:temsirolimus; D020123:Sirolimus
keywords: CNS tumors; Temsirolimus; bevacizumab; pediatric