Early Identification of Patients at Risk of Cabazitaxel-induced Severe Neutropenia.

Autor: Agema BC; Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands; Department of Clinical Pharmacy, Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address: b.agema@erasmusmc.nl., Buck SAJ; Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands., Viskil M; Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands., Isebia KT; Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands., de Neijs MJ; Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands., Sassen SDT; Department of Clinical Pharmacy, Erasmus University Medical Center, Rotterdam, The Netherlands; Rotterdam Clinical Pharmacometrics Group, Rotterdam, The Netherlands., Koch BCP; Department of Clinical Pharmacy, Erasmus University Medical Center, Rotterdam, The Netherlands; Rotterdam Clinical Pharmacometrics Group, Rotterdam, The Netherlands., Joerger M; Department of Medical Oncology and Hematology, Cantonal Hospital, St. Gallen, Switzerland., de Wit R; Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands., Koolen SLW; Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands; Department of Clinical Pharmacy, Erasmus University Medical Center, Rotterdam, The Netherlands., Mathijssen RHJ; Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands.
Jazyk: angličtina
Zdroj: European urology oncology [Eur Urol Oncol] 2024 Aug; Vol. 7 (4), pp. 786-793. Date of Electronic Publication: 2023 Nov 03.
DOI: 10.1016/j.euo.2023.10.015
Abstrakt: Background: Cabazitaxel frequently causes severe neutropenia. A higher cabazitaxel systemic exposure is related to a lower nadir absolute neutrophil count (ANC).
Objective: To describe the effect of cabazitaxel systemic exposure on ANC by a population pharmacokinetic/pharmacodynamic (POP-PK/PD) model, and to identify patients at risk of severe neutropenia early in their treatment course using a PK threshold.
Design, Setting, and Participants: Data from five clinical studies were pooled to develop a POP-PK/PD model using NONMEM, linking both patient characteristics and cabazitaxel systemic exposure directly to ANC.
Outcome Measurements and Statistical Analysis: A PK threshold, predictive of severe neutropenia (grade ≥3), was determined using a receiver operating characteristic curve.
Results and Limitations: Ninety-six patients were included with a total of 1726 PK samples and 1081 ANCs. The POP-PK/PD model described both cabazitaxel PK and ANC accurately. A cabazitaxel plasma concentration of >4.96 ng/ml at 6 h after the start of infusion was found to be predictive of severe neutropenia, with a sensitivity of 76% and a specificity of 65%.
Conclusions: Early cabazitaxel plasma levels are predictive of severe neutropenia. Implementation of the proposed PK threshold results in early identification of almost 76% of all severe neutropenias. If prospectively validated, patients at risk could benefit from prophylactic administration of granulocyte colony stimulating factors, preventing severe neutropenia in an early phase of treatment. Implementation of this threshold permits a less restricted use of the 25 mg/m 2 dose, potentially increasing the therapeutic benefit.
Patient Summary: Treatment with cabazitaxel chemotherapy often causes neutropenia, leading to susceptibility to infections, which might be life threatening. We found that a systemic cabazitaxel concentration above 4.96 ng/ml 6 h after the start of infusion is predictive of the occurrence of severe neutropenia. Measurement of systemic cabazitaxel levels provides clinicians with the opportunity to prophylactically stimulate neutrophil growth.
(Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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