Exposure to Docetaxel in the Elderly Patient Population: a Population Pharmacokinetic Study
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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.
KEY WORDSpharmacokinetics docetaxel older age prostate cancer
ACKNOWLEDGMENTS AND DISCLOSURES
No sources of funding were used in the preparation of this manuscript. Jos H. Beijnen is (part-time) employee and (indirect) shareholder of Modra Pharmaceuticals and (partly) holds a patent on oral taxane pharmaceutical formulations. The other authors declare no conflicts of interest in connection with this manuscript.
The authors wish to express their gratitude to all study participants and engaged medical workers (physicians and nurses) who made this work possible. The authors thank the Research High Performance Computing facility of the NKI for support in the use of computational resources. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committees and was carried out in accordance with ICH Guidelines for Good Clinical Practice. Written informed consent was obtained from all individual participants.
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