A Canadian paediatric brain tumour consortium (CPBTC) phase II molecularly targeted study of imatinib in recurrent and refractory paediatric central nervous system tumours Academic Article uri icon

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  • PURPOSE: To evaluate the safety, efficacy and pharmacokinetics of imatinib in children with recurrent or refractory central nervous system (CNS) tumours expressing KIT and/or PDGFRA. METHODS: Nineteen patients aged 2-18 years, with recurrent or refractory CNS tumours expressing either of the target receptors KIT and/or PDGFRA (by immunohistochemistry) were eligible. Participants received imatinib orally at a dose of 440 mg/m(2)/day and toxicities and tumour responses were monitored. Serial blood and cerebrospinal fluid samples for pharmacokinetics were obtained in a subset of consenting patients. Frozen tumour samples were analysed retrospectively for KIT and PDGFRA gene amplification in a subset of patients for whom samples were available. RESULTS: Common toxicities were lymphopaenia, neutropaenia, leucopaenia, elevated serum transaminases and vomiting. No intratumoural haemorrhages were observed. Although there were no objective responses to imatinib, four patients had long-term stable disease (SD) (38-104 weeks). Our results suggest a possible relationship between KIT expression and maintenance of SD with imatinib treatment; KIT immunopositivity was seen in only 58% (11/19) of study participants overall, but in 100% of patients with SD at 38 weeks. All patient tumours showed PDGFRA expression. Pharmacokinetic data showed a high interpatient variability, but corresponded with previously reported values. CONCLUSIONS: Imatinib at 440 mg/m(2)/day is relatively safe in children with recurrent CNS tumours, but induced no objective responses. Demonstration of SD in previously progressing patients (KIT-expressing) suggests cytostatic activity of imatinib.


  • Baruchel, Sylvain
  • Sharp, Julia R
  • Bartels, Ute
  • Hukin, Juliette
  • Odame, Isaac
  • Portwine, Carol
  • Strother, Doug
  • Fryer, Chris
  • Halton, Jackie
  • Egorin, Merrill J
  • Reis, Rui Manuel
  • Martinho, Olga
  • Stempak, Diana
  • Hawkins, Cynthia
  • Gammon, Janet
  • Bouffet, Eric

publication date

  • September 2009

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