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Annals of Oncology Advance Access published online on August 12, 2009
Annals of Oncology, doi:10.1093/annonc/mdp291
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© The Author 2009. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

review

Pharmacological management of gastrointestinal stromal tumours: an update on the role of sunitinib

J.-Y. Blay*

Léon Bérard Comprehensive Cancer Centre, Université Claude Bernard Lyon I, Lyon; Conticanet (FP6-018806), France; Soft Tissue and Bone Sarcoma Group of European Organisation for Research and Treatment of Cancer, Brussels, Belgium

* Correspondence to: Prof. J.-Y. Blay, Léon Bérard Comprehensive Cancer Centre, Université Claude Bernard Lyon I, 28 rue Laennec, F-69008 Lyon, France. Tel: +33-4-78-78-51-09; Fax: +33-4-78-78-27-16; E-mail: blay{at}lyon.fnclcc.fr

The efficacy and tolerability of the receptor tyrosine kinase inhibitor, sunitinib malate, have been demonstrated in phase I–III clinical trials of patients with imatinib-resistant or imatinib-intolerant gastrointestinal stromal tumours (GIST) as well as in a worldwide expanded-access study and in a continuous daily dosing (CDD) trial. Tumour genotype may have a significant influence on the activity of sunitinib in patients with imatinib-resistant GIST. Sunitinib activity was observed across different GIST genotypes and particularly in patients with wild-type and KIT exon 9 mutations (all relatively resistant to standard-dose imatinib) and in patients with secondary KIT exons 13 and 14 mutations. Adverse events with sunitinib were generally mild to moderate and easily managed by dose reduction, dose interruption or standard supportive measures. Treatment discontinuation can be avoided in most patients by close monitoring before and during treatment with appropriate adverse event management as necessary. The correlation between treatment exposure and clinical response is prompting the search for new approaches to treatment optimisation to ensure that patients derive maximum benefit from sunitinib therapy, including dose adjustments based on blood testing to ensure optimal drug exposure, and the use of the alternative CDD regimen to avoid treatment interruption.

adverse events, efficacy, gastrointestinal stromal tumours, KIT, resistance, sunitinib malate

Received for publication October 30, 2008. Revision received April 24, 2009. Accepted for publication April 24, 2009.


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