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Do pharmacokinetic polymorphisms explain treatment failure in high-risk patients with neuroblastoma?

Abstract：

PURPOSE:Neuroblastoma is the most common extracranial solid tumour in childhood. It accounts for 15% of all paediatric oncology deaths. In the last few decades, improvement in treatment outcome for high-risk patients has not occurred, with an overall survival rate <30-40%. Many reasons may account for such a low survival rate. The aim of this review is to evaluate whether pharmacogenetic factors can explain treatment failure in neuroblastoma. METHODS:A literature search based on PubMed's database Medical Subject Headings (MeSH) was performed to retrieve all pertinent publications on current treatment options and new classes of drugs under investigation. One hundred and fifty-eight articles wer reviewed, and relevant data were extracted and summarised. RESULTS AND CONCLUSIONS:Few of the large number of polymorphisms identified thus far showed an effect on pharmacokinetics that could be considered clinically relevant. Despite their clinical relevance, none of the single nucleotide polymorphisms (SNPs) investigated can explain treatment failure. These findings seem to reflect the clinical context in which anti-tumour drugs are used, i.e. in combination with multimodal therapy. In addition, many pharmacogenetic studies did not assess (differences in) drug exposure, which could contribute to explaining pharmacogenetic associations. Furthermore, it remains unclear whether the significant activity of new drugs on different neuroblastoma cell lines translates into clinical efficacy, irrespective of resistance or myelocytomatosis viral related oncogene, neuroblastoma derived (MYCN) amplification. Elucidation of the clinical role of pharmacogenetic factors in the treatment of neuroblastoma demands an integrated pharmacokinetic-pharmacodynamic approach to the analysis of treatment response data.

journal_name

Eur J Clin Pharmacol

journal_title

European journal of clinical pharmacology

authors

Bellanti F,Kågedal B,Della Pasqua O

doi

10.1007/s00228-010-0966-3

subject

Has Abstract

pub_date

2011-05-01 00:00:00

pages

87-107

eissn

0031-6970

issn

1432-1041

journal_volume

67 Suppl 1

pub_type

杂志文章,评审

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