Cmin公司
医学
主旨
伊马替尼
内科学
人口
比例危险模型
胃肠病学
肿瘤科
甲磺酸伊马替尼
间质细胞
最大值
药代动力学
环境卫生
髓系白血病
作者
Stéphane Bouchet,S. Poulette,Karine Titier,Nicholas Moore,Régis Lassalle,Abdelilah Abouelfath,Antoîne Italiano,Christine Chevreau,Emmanuelle Bompas,Olivier Collard,Florence Duffaud,María Rios,Didier Cupissol,Antoine Adenis,Isabelle Ray‐Coquard,Olivier Bouché,Axel Le Cesne,Binh Bui,Jean‐Yves Blay,Mathiéu Molimard
标识
DOI:10.1016/j.ejca.2015.12.029
摘要
Background Imatinib has dramatically improved the prognosis of advanced gastrointestinal stromal tumours (GISTs). Clinical trial data showed that patients with trough imatinib plasma concentrations (Cmin) below 1100 ng/ml (quartile 1) had shorter time to progression, but no threshold has been defined. The main objective of this study was to investigate in advanced GIST whether a Cmin threshold value associated with a longer progression-free survival (PFS) could be specified. This would be the first step leading to therapeutic drug monitoring of imatinib in GIST. Patients and methods Advanced GIST patients (n=96) treated with imatinib 400 mg/d (41 stomach, 34 small bowel, and 21 other primary site localisations) were prospectively included in this real-life setting study. Routine plasma level testing imatinib (Cmin) and clinical data of were recorded prospectively. Results Small bowel localisation was associated with an increased relative risk of progression of 3.09 versus stomach localisation (p=0.0255). Mean Cmin (±standard deviation) was 868 (±536) ng/ml with 75% inter-individual and 26% intra-patient variability. A Cmin threshold of 760 ng/ml defined by log-rank test was associated with longer PFS for the whole population (p=0.0256) and for both stomach (p=0.043) and small bowel (p=0.049) localisations when analysed separately. Multivariate Cox regression analysis found that Cmin above 760 ng/ml was associated with 65% reduction risk of progression (p=0.0271) in the whole population independently of the anatomical localisation. Conclusion Concentration of imatinib significantly influences duration of tumour control treatment in GIST patients with a Cmin threshold of 760 ng/ml associated with prolonged PFS in real-life setting.
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