ArticleInvestigational new drugs2012
A simultaneous analysis of the time-course of leukocytes and neutrophils following docetaxel administration using a semi-mechanistic myelosuppression model.
Article in Investigational new drugs, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Immune-related adverse events associated with nab-paclitaxel/paclitaxel combined with immune checkpoint inhibitors: a systematic review and network meta-analysis.Frontiers in immunology · 2023Pooled it
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- Pharmacokinetic/Pharmacodynamic modeling of abexinostat-induced thrombocytopenia across different patient populations: application for the determination of the maximum tolerated doses in both lymphoma and solid tumour patients.Investigational new drugs · 2014Trial
- Development of a simplified population pharmacokinetic-pharmacodynamic framework for exposure-informed risk stratification of neutropenia during amrubicin treatment.Cancer chemotherapy and pharmacology · 2026Article
- Efficacy and safety of asunercept, a CD95L-selective inhibitor, in hospitalised patients with moderate-to-severe COVID-19: ASUNCTIS, a multicentre, randomised, open-label, controlled, phase 2 trial.EClinicalMedicine · 2024Article
- Clinical decision support for chemotherapy-induced neutropenia using a hybrid pharmacodynamic/machine learning model.CPT: pharmacometrics & systems pharmacology · 2023Article
- Chemo-Immunotherapy: A New Trend in Cancer Treatment.Cancers · 2023Review
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- Should personalised dosing have a role in cancer treatment?Frontiers in oncology · 2023Article
- Moving Immune Checkpoint Inhibitors to Early Non-Small Cell Lung Cancer: A Narrative Review.Cancers · 2022Review
- Chemotherapy reinforces anti-tumor immune response and enhances clinical efficacy of immune checkpoint inhibitors.Frontiers in oncology · 2022Review
- Systems Modeling to Quantify Safety Risks in Early Drug Development: Using Bifurcation Analysis and Agent-Based Modeling as Examples.The AAPS journal · 2021Review
- Model-Based Simulation of Maintenance Therapy of Childhood Acute Lymphoblastic Leukemia.Frontiers in physiology · 2020Article
- Individual optimal dose of amrubicin to prevent severe neutropenia in Japanese patients with lung cancer.Cancer science · 2019Article
- Mathematical models for cytarabine-derived myelosuppression in acute myeloid leukaemia.PloS one · 2019Article
- Pharmacokinetic-pharmacodynamic modelling of neutrophil response to G-CSF in healthy subjects and patients with chemotherapy-induced neutropenia.British journal of clinical pharmacology · 2018Article
- Transit and lifespan in neutrophil production: implications for drug intervention.Journal of pharmacokinetics and pharmacodynamics · 2018Article
- Population Pharmacokinetic-Pharmacodynamic Modeling of 5-Fluorouracil for Toxicities in Rats.European journal of drug metabolism and pharmacokinetics · 2017Article
- Advanced Methods for Dose and Regimen Finding During Drug Development: Summary of the EMA/EFPIA Workshop on Dose Finding (London 4-5 December 2014).CPT: pharmacometrics & systems pharmacology · 2017Article
- Article
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo improve the predictive capacity of a semi-mechanistic myelosuppression model for neutrophils as the model have shown to over-predict the nadir of neutrophils and, secondly, to develop a model describing the time-course of leukocytes and neutrophils simultaneously. EXPERIMENTAL
designThe study included 601 cancer patients treated with a 1 h infusion of docetaxel in monotherapy. A total of 3,549 pairwise observations of leukocytes and neutrophils from one treatment cycle were analyzed simultaneously in NONMEM.
resultsA basic model was developed consisting of a neutrophil and a non-neutrophil model, each with the same structure as the semi-mechanistic myelosuppression model. The leukocytes were modeled as the sum of the predicted neutrophils and non-neutrophils. The model described the time-course of the leukocytes well, but was not able to capture the nadir of the neutrophils. Hence the model was further refined and the included modifications (p < 0.001) in the final model are a sigmoid Emax functions for the drug effect, feedback functions on the cell maturation time in bone-marrow and an optimized number of transit compartments for each of the two cell types.
conclusionsA joint semi-mechanistic myelosuppression model describing the time-course of leukocytes and neutrophils following docetaxel administration was developed. The data supported a more complex model compared to the previous model developed by Friberg et al. (2002), and increased the model's capacity to accurately describe the time-course of neutrophils following docetaxel therapy. The combined model also illustrates the differences between the cell types and allows prediction of neutrophil counts from leukocyte measurements.
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Registered trials
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