Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek - Netherlands Cancer Institute, Plesmanlaan 121, 1066, CX, Amsterdam, the Netherlands.
Division of Pharmacology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
Pharm Res. 2019 Nov 15;36(12):181. doi: 10.1007/s11095-019-2706-4.
Docetaxel is commonly used in elderly patients, who are frequently diagnosed with prostate cancer. Although previous studies revealed no clinically relevant impact of older age on docetaxel pharmacokinetics (PK), this may be masked by indication. Metastatic castration-resistant prostate cancer (mCRPC) patients were reported to have approximately two-times lower systemic exposure compared to patients with other solid tumors. This study assessed the impact of older age on docetaxel PK, also considering the effect of indication on docetaxel PK.
Prospectively collected docetaxel PK data from patients aged ≥70 was pooled with PK data from an earlier published multicenter study. A 3-compartment population PK model, including multiple covariates, was used to describe docetaxel plasma concentration-time data. We added the effect of prostate cancer (mCRPC and metastatic hormone-sensitive prostate cancer (mHSPC)) on clearance to this model. Hereafter, we evaluated the additional impact of older age on docetaxel clearance, using a significance threshold of p < 0.005.
Docetaxel plasma concentration-time data from 157 patients were analyzed. Median age in the total cohort was 67 years (range 31-87), with 49% of the total cohort aged ≥70. The impact of age on docetaxel clearance was statistically significant (p < 0.005). For a typical patient, a 10-year and 20-year increase of age led to a reduction in clearance of 17% and 34%, respectively.
In this cohort study, age significantly and independently affected docetaxel clearance, showing lower docetaxel clearance in elderly patients. In our cohort, mCRPC and mHSPC patients both had higher clearance than patients with other solid tumors.
多西他赛常用于老年患者，这些患者常被诊断为前列腺癌。尽管之前的研究表明，年龄对多西他赛药代动力学（PK）没有临床相关影响，但这可能被适应证所掩盖。转移性去势抵抗性前列腺癌（mCRPC）患者的全身暴露量比其他实体瘤患者低约两倍。本研究评估了年龄对多西他赛 PK 的影响，同时还考虑了适应证对多西他赛 PK 的影响。
我们对年龄≥70 岁的患者的多西他赛 PK 数据进行了前瞻性收集，并与先前发表的多中心研究的 PK 数据进行了汇总。使用包含多个协变量的三房室群体 PK 模型来描述多西他赛的血浆浓度-时间数据。我们在此模型中添加了前列腺癌（mCRPC 和转移性激素敏感性前列腺癌（mHSPC））对清除率的影响。此后，我们使用 p 值<0.005 的显著性阈值评估年龄对多西他赛清除率的额外影响。
共分析了 157 例患者的多西他赛血浆浓度-时间数据。总队列的中位年龄为 67 岁（范围 31-87），其中 49%的患者年龄≥70 岁。年龄对多西他赛清除率的影响具有统计学意义（p<0.005）。对于一般患者，年龄每增加 10 年和 20 年，清除率分别降低 17%和 34%。
在本队列研究中，年龄显著且独立地影响了多西他赛的清除率，表现为老年患者的多西他赛清除率较低。在本队列中，mCRPC 和 mHSPC 患者的清除率均高于其他实体瘤患者。
