ArticleActa pharmacologica Sinica2016
Preclinical PK/PD model for combined administration of erlotinib and sunitinib in the treatment of A549 human NSCLC xenograft mice.
Article in Acta pharmacologica Sinica, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 26 citations in OpenAlex.
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- Identification of oncology pharmacokinetic drivers through in vitro experiments and computational modeling.Journal of pharmacokinetics and pharmacodynamics · 2025Article
- Model-Based Evaluation of HangAmDan-B1 and Afatinib Combination Therapy in HCC827 Xenograft Mice with Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Antineoplastic indole-containing compounds with potential VEGFR inhibitory properties.RSC advances · 2024Review
- Pharmacokinetic/Pharmacodynamic Analysis of Savolitinib plus Osimertinib in an EGFR Mutation-Positive, MET-Amplified Non-Small Cell Lung Cancer Model.Molecular cancer therapeutics · 2023Article
- Amplification of anticancer efficacy by co-delivery of doxorubicin and lonidamine with extracellular vesicles.Drug delivery · 2022Article
- Modeling restoration of gefitinib efficacy by co-administration of MET inhibitors in an EGFR inhibitor-resistant NSCLC xenograft model: A tumor-in-host DEB-based approach.CPT: pharmacometrics & systems pharmacology · 2021Article
- A Dynamic Energy Budget (DEB) based modeling framework to describe tumor-in-host growth inhibition and cachexia onset during anticancer treatment inOncotarget · 2021Article
- A Novel Integrated Pharmacokinetic-Pharmacodynamic Model to Evaluate Combination Therapy and DetermineThe Journal of pharmacology and experimental therapeutics · 2021Article
- Delivery of oligonucleotide-based therapeutics: challenges and opportunities.EMBO molecular medicine · 2021Review
- Pharmacokinetic-Pharmacodynamic Modeling of Tumor Targeted Drug Delivery Using Nano-Engineered Mesenchymal Stem Cells.Pharmaceutics · 2021Article
- Model-Based Anticancer Effect of Botulinum Neurotoxin Type A1 on Syngeneic Melanoma Mice.Frontiers in pharmacology · 2021Article
- Different ODE models of tumor growth can deliver similar results.BMC cancer · 2020Article
- Semi-Mechanistic Modeling of HY-021068 Based on Irreversible Inhibition of Thromboxane Synthetase.Frontiers in pharmacology · 2020Article
- Antitumor effect of axitinib combined with dopamine and PK-PD modeling in the treatment of human breast cancer xenograft.Acta pharmacologica Sinica · 2019Article
- Survival Prolongation Index as a Novel Metric to Assess Anti-Tumor Activity in Xenograft Models.The AAPS journal · 2019Article
- Time-dependent pharmacokinetics of dexamethasone and its efficacy in human breast cancer xenograft mice: a semi-mechanism-based pharmacokinetic/pharmacodynamic model.Acta pharmacologica Sinica · 2018Article
- Pharmacokinetic-Pharmacodynamic Modeling of the Anti-Tumor Effect of Sunitinib Combined with Dopamine in the Human Non-Small Cell Lung Cancer Xenograft.Pharmaceutical research · 2017Article
- Mathematical model on Alzheimer's disease.BMC systems biology · 2016Article
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Authors and funding
10 authors at 1 institution in 1 country.
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Abstract
aimCombined therapy of EGFR TKI and VEGFR TKI may produce a greater therapeutic benefit and overcome EGFR TKI-induced resistance. However, a previous study shows that a combination of EGFR TKI erlotinib (ER) with VEGFR TKI sunitinib (SU) did not improve the overall survival in patients with non-small-cell lung cancer (NSCLC). In this study we examined the anticancer effect of ER, SU and their combination in the treatment of A549 human NSCLC xenograft mice, and conducted PK/PD modeling and simulations to optimize the dose regimen.
methodsER (20, 50 mg·kg(-1)·d(-1)) or SU (5, 10, 20 mg·kg(-1)·d(-1)) alone, or their combination were administered to BALB/c nude mice bearing A549 tumors for 22 days. The tumor size and body weight were recorded daily. The experimental data were used to develop PK/PD models describing the quantitative relationship between the plasma concentrations and tumor suppression in different dose regimens. The models were further evaluated and validated, and used to predict the efficacy of different combination regimens and to select the optimal regimen.
resultsThe in vivo anticancer efficacy of the combination groups was much stronger than that of either drug administered alone. A PK/PD model was developed with a combination index (φ) of 4.4, revealing a strong synergistic effect between ER and SU. The model simulation predicted the tumor growth in different dosage regimens, and showed that the dose of SU played a decisive role in the combination treatment, and suggested that a lower dose of ER (≤5 mg·kg(-1)·d(-1)) and adjusting the dose of SU might yield a better dosage regimen for clinical research.
conclusionThe experimental data and modeling confirm synergistic anticancer effect of ER and SU in the treatment of A549 xenograft mice. The optimal dosage regimen determined by the PK/PD modeling and simulation can be used in future preclinical study and provide a reference for clinical application.
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