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.

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.

• Authors: Sarina A Piha-Paul, Sang Joon Shin, Tribhawan Vats, Nandita Guha-Thakurta, Joann Aaron, Michael Rytting, Eugenie Kleinerman, Razelle Kurzrock
• Journal: Anticancer research (Anticancer Res) Vol. 34 Issue 4 Pg. 1939-45 (Apr 2014) ISSN: 1791-7530 [Electronic] Greece
• PMID: 24692729 (Publication Type: Clinical Trial, Phase I, Journal Article)

Chemical References

• Angiogenesis Inhibitors
• Antibodies, Monoclonal, Humanized
• Protein Kinase Inhibitors
• Bevacizumab
• temsirolimus
• Sirolimus

Topics

• Adolescent
• Angiogenesis Inhibitors (administration & dosage)
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Bevacizumab
• Brain Neoplasms (diagnosis, therapy)
• Central Nervous System Neoplasms (diagnosis, drug therapy, therapy)
• Child
• Child, Preschool
• Humans
• Magnetic Resonance Imaging
• Protein Kinase Inhibitors (administration & dosage)
• Sirolimus (administration & dosage, analogs & derivatives)
• Treatment Outcome