CHU Besançon, Laboratoire de Pharmacologie Clinique, Hôpital Jean Minjoz, 25030 Besançon, France.
Fundam Clin Pharmacol. 2011 Aug;25(4):414-24. doi: 10.1111/j.1472-8206.2010.00874.x. Epub 2010 Sep 9.
Taxanes are anticancer drugs on the market for more than 10 years that are thought to be interesting for therapeutic drug monitoring (TDM): high inter- and intra-patient variability, relationship between exposure and efficacy and especially toxicity. Nevertheless, the paclitaxel and docetaxel characteristics result in different conclusions for these two molecules with respect to their TDM. For paclitaxel, the nonlinear pharmacokinetics makes that the parameter which seems the more reliable to toxicity or outcome is the time during which the plasma concentration exceeds 0.05 μm. Concentration controlled studies using Bayesian adaptation showed that the TDM of paclitaxel is feasible in routine. However, this target needs to be prospectively validated with new weekly schedules of administration, leading to a balance between 'recommended' and 'potentially useful'. For docetaxel, the 3-weekly administration, which is the more effective scheme, is also the more toxic. However, neutropenia can be individually modeled and efficiently predicted without using plasma drug concentrations. The docetaxel TDM using this docetaxel-related neutropenia modeling however needs to be prospectively validated in routine. The level of evidence of TDM thus 'needs to be assessed'.
紫杉烷类药物是上市超过 10 年的抗癌药物，被认为是治疗药物监测（TDM）的候选药物：患者间和患者内的变异性大，暴露与疗效，特别是毒性之间存在关联。然而，紫杉醇和多西紫杉醇的特点导致这两种分子的 TDM 结果不同。对于紫杉醇来说，药代动力学是非线性的，因此似乎与毒性或疗效更相关的参数是血浆浓度超过 0.05μm 的时间。使用贝叶斯自适应的浓度控制研究表明，紫杉醇的 TDM 在常规情况下是可行的。然而，这一目标需要通过新的每周给药方案进行前瞻性验证，以在“推荐”和“可能有用”之间取得平衡。对于多西紫杉醇，3 周一次的给药方案是更有效的方案，也是毒性更大的方案。然而，中性粒细胞减少症可以通过不使用血浆药物浓度进行个体化建模和有效地预测。然而，使用这种与多西紫杉醇相关的中性粒细胞减少症建模的多西紫杉醇 TDM 需要在常规情况下进行前瞻性验证。因此，TDM 的证据水平“需要进行评估”。
