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A Pharmacometric Model to Predict Chemotherapy-Induced Myelosuppression and Associated Risk Factors in Non-Small Cell Lung Cancer

Authors
 Kyemyung Park  ;  Yukyung Kim  ;  Mijeong Son  ;  Dongwoo Chae  ;  Kyungsoo Park 
Citation
 PHARMACEUTICS, Vol.14(5) : 914, 2022-04 
Journal Title
PHARMACEUTICS
Issue Date
2022-04
Keywords
K-PD model ; R Shiny ; chemotherapy ; cisplatin ; myelosuppression ; neutropenia ; non-small cell lung cancer ; paclitaxel ; pharmacokinetic and pharmacodynamic modeling ; transit compartments
Abstract
Chemotherapy often induces severe neutropenia due to the myelosuppressive effect. While predictive pharmacokinetic (PK)/pharmacodynamic (PD) models of absolute neutrophil count (ANC) after anticancer drug administrations have been developed, their deployments to routine clinics have been limited due to the unavailability of PK data and sparseness of PD (or ANC) data. Here, we sought to develop a model describing temporal changes of ANC in non-small cell lung cancer patients receiving (i) combined chemotherapy of paclitaxel and cisplatin and (ii) granulocyte colony stimulating factor (G-CSF) treatment when needed, under such limited circumstances. Maturation of myelocytes into blood neutrophils was described by transit compartments with negative feedback. The K-PD model was employed for drug effects with drug concentration unavailable and the constant model for G-CSF effects. The fitted model exhibited reasonable goodness of fit and parameter estimates. Covariate analyses revealed that ANC decreased in those without diabetes mellitus and female patients. Using the final model obtained, an R Shiny web-based application was developed, which can visualize predicted ANC profiles and associated risk of severe neutropenia for a new patient. Our model and application can be used as a supportive tool to identify patients at the risk of grade 4 neutropenia early and suggest dose reduction.
Files in This Item:
T202201576.pdf Download
DOI
10.3390/pharmaceutics14050914
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Park, Kyungsoo(박경수) ORCID logo https://orcid.org/0000-0002-6972-1143
Chae, Dong Woo(채동우) ORCID logo https://orcid.org/0000-0002-7675-3821
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/188823
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