Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study.

摘要: Summary Background Gastrointestinal stromal tumours (GISTs) are rare of the gastrointestinal tract characterised by cell-surface expression tyrosine kinase KIT (CD117). No effective systemic treatment is available. Imatinib (STI571) inhibits a similar kinase, BCR-ABL, leading to responses in chronic myeloid leukaemia, and has also been shown inhibit KIT. We did phase I study identify dose-limiting toxic effects imatinib patients with advanced soft tissue sarcomas including GISTs. Methods 40 (of whom 36 had GISTs) received at doses 400 mg once daily, 300 twice or 500 daily. Toxic haematological, biochemical, radiological measurements were assessed during 8 weeks follow-up. 18 Fluorodeoxy-glucose positron-emission tomography (PET) was used for response assessment one centre. Findings Five on daily (severe nausea, vomiting, oedema, rash). Inhibition tumour growth seen all but four GISTs, resulting 19 confirmed partial six as yet unconfirmed more than 20% regressions. 24 27 clinically symptomatic showed improvement, 29 still after 9 months. PET scan predicted subsequent computed responses. Interpretation dose well tolerated first weeks, side-effects diminish continuing treatment, it significant activity Our results provide evidence role show potential development anticancer drugs based specific molecular abnormalities present cancers.