Imatinib in advanced gastrointestinal stromal tumour: when is 800 mg the correct dose?
OBJECTIVE
Gastrointestinal stromal tumour patients with exon 9 KIT mutations have a worse outcome, but progression-free survival is improved by treatment with imatinib 800 mg daily. This review looks at the evidence and asks whether this should be standard treatment from diagnosis.


RESULTS
The phase III trial in advanced gastrointestinal stromal tumour, EORTC 62005, demonstrated increased progression-free survival for imatinib 800 mg daily versus 400 mg. Mutational analysis showed the benefit was primarily due to patients with exon 9 mutations. A meta-analysis has confirmed this finding. Patients who progress on standard dose imatinib may also experience disease stabilization. The significance of this in relation to data on pharmacokinetics and secondary mutations will be discussed.


CONCLUSIONS
Mutational analysis of KIT and PDGFRA should ideally be performed in all patients with advanced gastrointestinal stromal tumour. Patients with mutations in exon 9 of KIT should be considered for treatment with imatinib 800 mg daily, but current data do not indicate whether there is a survival advantage for immediate treatment at 800 mg. There still appears to be a role for the higher dose in patients progressing after an initial response to the standard dose therapy.
Judson
Ian
I
Sarcoma Unit, Royal Marsden Hospital, London, UK. Ian.Judson@icr.ac.uk
D001549:Benzamides; D004305:Dose-Response Relationship, Drug; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy*; D006801:Humans; D000068877:Imatinib Mesylate; D010879:Piperazines / Q000008:administration & dosage*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000008:administration & dosage*
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases