Bouchet Stéphane, Royer Bernard, Le Guellec Chantal, Titier Karine
CHU Pellegrin, Université de Bordeaux, Bordeaux, France.
Therapie. 2010 May-Jun;65(3):213-8. doi: 10.2515/therapie/2010017. Epub 2010 Aug 11.
During the last decade, imatinib was current gold standard treatment of chronic myelogenous leukemia (CML), showing a great effectiveness. Thus, the Therapeutic Drug Monitoring (TDM), rarely applied in clinical oncology practice, did not appear necessary at the moment. However, the absence of response among patients and the metabolic profile of imatinib (involving the CYP3A4) suggested the existence of a great interindividual variability. During the last 4 years, studies about the pharmacokinetic/pharmacodynamic relationship have confirmed this variability and highlighted a relation between the trough concentrations of imatinib and the clinical response. An effectiveness threshold, close to 1000 ng/mL, seems to be correlated with better cytogenetic and molecular responses. Consequently, TDM could assist in investigation of the observance, the absence of response, the drug-drug interactions, but the proof of its utility requires complementary studies. In conclusion, the level of proof of imatinib TDM in LMC varies between levels "recommended" and "potentially useful".
在过去十年中，伊马替尼是慢性粒细胞白血病（CML）的现行金标准治疗药物，显示出巨大的疗效。因此，治疗药物监测（TDM）在临床肿瘤学实践中很少应用，目前似乎没有必要。然而，患者中缺乏反应以及伊马替尼的代谢特征（涉及CYP3A4）表明存在很大的个体间差异。在过去4年中，关于药代动力学/药效学关系的研究证实了这种差异，并突出了伊马替尼谷浓度与临床反应之间的关系。接近1000 ng/mL的有效性阈值似乎与更好的细胞遗传学和分子反应相关。因此，TDM有助于调查服药依从性、无反应情况、药物相互作用，但证明其效用需要补充研究。总之，伊马替尼TDM在慢性粒细胞白血病中的证据水平在“推荐”和“可能有用”之间有所不同。
