Predicting the active doses in humans from animal studies: A novel approach in oncology

Rocchetti, Maurizio; Simeoni, Monica; Pesenti, Enrico; Nicolao, Giuseppe De; Poggesi, Italo

doi:10.1016/j.ejca.2007.05.011

Cited by 85 publications

(61 citation statements)

References 23 publications

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“…No generally accepted methodologies for extrapolating the in vivo evaluation in animal models to human are currently available although many statistical methods have been attempted [27] . The poor reliability is reported mainly due to the interspecies differences [27] .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Subacute oral toxicity study of ethanolic leaves extracts of Strobilanthes crispus in rats

Lim

Chin

2012

Asian Pacific Journal of Tropical Biomedicine

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Section: Discussionmentioning

confidence: 99%

“…The poor reliability is reported mainly due to the interspecies differences [27] . Additional information needs to be considered in designing animal studies in order to predict the similar effects might be anticipated in human.…”

Section: Discussionmentioning

confidence: 99%

Subacute oral toxicity study of ethanolic leaves extracts of Strobilanthes crispus in rats

Lim

Chin

2012

Asian Pacific Journal of Tropical Biomedicine

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“…Exponential-linear model [1], [10], [11] is an empirical method to analyze the tumor cell proliferation quantitatively based on parameters defined for exponential and linear phases of tumor growth. We build artificial intelligence based mathematical models to compute tumor growth and related parameters including exponential-linear model parameters.…”

Section: Modeling Tumor Growthmentioning

confidence: 99%

“…The centroid nuclei set consists of centroids of the clusters for integer and can be computed as: (8) where the nucleus and is the dimension of cluster . Using the centroids of k number of clusters and the remaining nuclei in Euclidian space where , we compute average of intra distances between the centroids and all other nuclei of the same clusters: (9) and the minimum inter distance between nuclei cluster centroids: (10) where integer and integer identify the compactness and separation of clusters, respectively. The minimum of the distances between centroids (i.e.…”

Section: B Nuclei Clustersmentioning

confidence: 99%

Modeling Tumor Growth for Kidney Cancer Based on Nuclei Clusters of Pathology Slides

Saribudak¹,

Dong²,

Hsieh³

et al. 2016

IJET

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“…To describe this phenomenon in this study, some transit compartments with the same first-order transit rate k 1 were applied, as recommended by Jusko and Savic [25,26] . The number of transit compartments was always 3 in the previous study [27,28] , and we used different transit compartment numbers from 0 to 4 to investigate model fitting. Ultimately, the PK/PD model of the ER group and the combination group included 3 compartments, and the model of the SU group contained one compartment.…”

Section: Wwwchinapharcom LI Jy Et Almentioning

confidence: 99%

Preclinical PK/PD model for combined administration of erlotinib and sunitinib in the treatment of A549 human NSCLC xenograft mice

Ren

Yin

et al. 2016

Acta Pharmacol Sin

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Aim: Combined 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. Methods: ER (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. Results: The 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. Conclusion: The 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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Predicting the active doses in humans from animal studies: A novel approach in oncology

Cited by 85 publications

References 23 publications

Subacute oral toxicity study of ethanolic leaves extracts of Strobilanthes crispus in rats

Subacute oral toxicity study of ethanolic leaves extracts of Strobilanthes crispus in rats

Modeling Tumor Growth for Kidney Cancer Based on Nuclei Clusters of Pathology Slides

Preclinical PK/PD model for combined administration of erlotinib and sunitinib in the treatment of A549 human NSCLC xenograft mice

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