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A Canadian paediatric brain tumour consortium (CPBTC) phase II molecularly targeted study of imatinib in recurrent and refractory paediatric central nervous system tumours
European Journal of Cancer, 06/26/09

Baruchel S et al. - In a study 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, it was concluded that imatinib at 440 mg/m2/day is relatively safe in children with recurrent CNS tumours, but induced no objective responses. Demonstration of stable disease (SD) in previously progressing pts (KIT-expressing) suggests cytostatic activity of imatinib.

• 19 pts aged 2–18 yrs, 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/m2/day and toxicities and tumour responses were monitored.
• Serial blood and cerebrospinal fluid samples for pharmacokinetics were obtained in a subset of consenting pts.
• Frozen tumour samples were analysed retrospectively for KIT and PDGFRA gene amplification in a subset of pts for whom samples were available.

• Common toxicities were lymphopaenia, neutropaenia, leucopaenia, elevated serum transaminases, and vomiting.
• No intratumoural haemorrhages were observed.
• Although there were no objective responses to imatinib, 4 pts had long-term stable disease (SD) (38–104 wks).
• 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 pts with SD at 38 wks.
• All pt tumours showed PDGFRA expression.
• Pharmacokinetic data showed a high interpatient variability, but corresponded with previously reported values.

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