Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/50283
Título: | A Canadian paediatric brain tumour consortium (CPBTC) phase II molecularly targeted study of imatinib in recurrent and refractory paediatric central nervous system tumours |
Autor(es): | Baruchel, Sylvain Sharp, Julia R. Bartels, Ute Hukin, Juliette Odame, Isaac Portwine, Carol Strother, Doug Fryer, Chris Reis, R. M. Martinho, Olga |
Palavras-chave: | Imatinib Paediatrics Phase II Central nervous system neoplasms Brain neoplasms Platelet-derived growth factor alpha receptor C-kit Drug toxicity Pharmacokinetics |
Data: | Set-2009 |
Editora: | Elsevier 1 |
Revista: | European Journal of Cancer |
Resumo(s): | 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. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/50283 |
DOI: | 10.1016/j.ejca.2009.05.008 |
ISSN: | 0959-8049 |
Versão da editora: | https://www.sciencedirect.com/science/article/pii/S0959804909003487 |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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baruchel s_ eur j cancer 2009.pdf | 141,46 kB | Adobe PDF | Ver/Abrir |