Neutropenia and docetaxel exposure in metastatic castration-resistant prostate cancer patients: A meta-analysis and evaluation of a clinical cohort.
docetaxel
exposure
meta-analysis
neutropenia
prostate cancer
Journal
Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
27
07
2018
revised:
09
01
2019
accepted:
13
01
2019
pubmed:
26
2
2019
medline:
8
5
2020
entrez:
26
2
2019
Statut:
ppublish
Résumé
The incidence of neutropenia in metastatic castration-resistant prostate cancer (mCRPC) patients treated with docetaxel has been reported to be lower compared to patients with other solid tumors treated with a similar dose. It is suggested that this is due to increased clearance of docetaxel in mCRPC patients, resulting in decreased exposure. The aims of this study were to (1) determine if exposure in mCRPC patients is lower vs patients with other solid tumors by conducting a meta-analysis, (2) evaluate the incidence of neutropenia in patients with mCRPC vs other solid tumors in a clinical cohort, and (3) discuss potential clinical consequences. A meta-analysis was conducted of studies which reported areas under the plasma concentration-time curves (AUCs) of docetaxel and variability. In addition, grade 3/4 neutropenia was evaluated using logistic regression in a cohort of patients treated with docetaxel. The meta-analysis included 36 cohorts from 26 trials (n = 1150 patients), and showed that patients with mCRPC had a significantly lower mean AUC vs patients with other solid tumors (fold change [95% confidence interval (CI)]: 1.8 [1.5-2.2]), with corresponding AUCs of 1.82 and 3.30 mg∙h/L, respectively. Logistic regression, including 812 patient, demonstrated that patients with mCRPC had a 2.2-fold lower odds of developing grade 3/4 neutropenia compared to patients with other solid tumors (odds ratio [95%CI]: 0.46 [0.31-0.90]). These findings indicate that mCRPC patients have a lower risk of experiencing severe neutropenia, possibly attributable to lower systemic exposure to docetaxel.
Identifiants
pubmed: 30802002
doi: 10.1002/cam4.2003
pmc: PMC6488109
doi:
Substances chimiques
Docetaxel
15H5577CQD
Types de publication
Comparative Study
Journal Article
Meta-Analysis
Langues
eng
Sous-ensembles de citation
IM
Pagination
1406-1415Informations de copyright
© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
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