Title
Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours : a phase I study
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
London ,
Subject
Human medicine
Source (journal)
The lancet : international edition. - London, 1823, currens
Volume/pages
358(2001) :9291 , p. 1421-1423
ISSN
0140-6736
1474-547X
ISI
000171940100014
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Abstract
Background Gastrointestinal stromal tumours (GISTs) are rare tumours of the gastrointestinal tract characterised by cell-surface expression of the tyrosine kinase KIT (CD117). No effective systemic treatment is available. Imatinib (STI571) inhibits a similar tyrosine kinase, BCR-ABL, leading to responses in chronic myeloid leukaemia, and has also been shown to inhibit KIT. We did a phase I study to identify the dose-limiting toxic effects of imatinib in patients with advanced soft tissue sarcomas including GISTs. Methods 40 patients (of whom 36 had GISTs) received imatinib at doses of 400 mg once daily, 300 mg twice daily, 400 mg twice daily, or 500 mg twice daily. Toxic effects and haematological, biochemical, and radiological measurements were assessed during 8 weeks of follow-up.18 Fluorodeoxy-glucose positron-emission tomography (PET) was used for response assessment in one centre. Findings Five patients on 500 mg imatinib twice daily had dose-limiting toxic effects (severe nausea, vomiting, oedema, or rash). Inhibition of tumour growth was seen in all but four patients with GISTs, resulting in 19 confirmed partial responses and six as yet unconfirmed partial responses or more than 20% regressions. 24 of 27 clinically symptomatic patients showed improvement, and 29 of 36 were still on treatment after more than 9 months. PET scan responses predicted subsequent computed tomography responses. Interpretation Imatinib at a dose of 400 mg twice daily is well tolerated during the first 8 weeks, side-effects diminish with continuing treatment, and it has significant activity in patients with advanced GISTs. Our results provide evidence of a role for KIT in GISTs, and show the potential for the development of anticancer drugs based on specific molecular abnormalities present in cancers.
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