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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.

Methods

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.

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, 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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