Marie-Rose B S Crombag1,2, Thomas P C Dorlo3,4, Ellen van der Pan4, Anoek van Straten4, Andries M Bergman5, Nielka P van Erp6, Jos H Beijnen3,4,7, Alwin D R Huitema3,4,8. 1. Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek - Netherlands Cancer Institute, Plesmanlaan 121, 1066, CX, Amsterdam, the Netherlands. m.crombag@nki.nl. 2. Division of Pharmacology, Netherlands Cancer Institute, Amsterdam, the Netherlands. m.crombag@nki.nl. 3. Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek - Netherlands Cancer Institute, Plesmanlaan 121, 1066, CX, Amsterdam, the Netherlands. 4. Division of Pharmacology, Netherlands Cancer Institute, Amsterdam, the Netherlands. 5. Division of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. 6. Department of Pharmacy and Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands. 7. Utrecht Institute for Pharmaceutical Sciences (UIPS), Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, the Netherlands. 8. Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: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. METHODS: 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. RESULTS: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. CONCLUSION: 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.
Entities:
Keywords:
docetaxel; older age; pharmacokinetics; prostate cancer
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