Revisiting bevacizumab + cytotoxics scheduling using mathematical modeling: proof of concept study in experimental non-small cell lung carcinoma
IMBS, Diane-Charlotte
Simulation & Modelling : Adaptive Response for Therapeutics in Cancer [SMARTc unit]
Simulation & Modelling : Adaptive Response for Therapeutics in Cancer [SMARTc unit]
EL CHEIKH, Raouf
Simulation & Modelling : Adaptive Response for Therapeutics in Cancer [SMARTc unit]
Simulation & Modelling : Adaptive Response for Therapeutics in Cancer [SMARTc unit]
BOYER, Arnaud
Simulation & Modelling : Adaptive Response for Therapeutics in Cancer [SMARTc unit]
Service d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM]
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Simulation & Modelling : Adaptive Response for Therapeutics in Cancer [SMARTc unit]
Service d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM]
IMBS, Diane-Charlotte
Simulation & Modelling : Adaptive Response for Therapeutics in Cancer [SMARTc unit]
Simulation & Modelling : Adaptive Response for Therapeutics in Cancer [SMARTc unit]
EL CHEIKH, Raouf
Simulation & Modelling : Adaptive Response for Therapeutics in Cancer [SMARTc unit]
Simulation & Modelling : Adaptive Response for Therapeutics in Cancer [SMARTc unit]
BOYER, Arnaud
Simulation & Modelling : Adaptive Response for Therapeutics in Cancer [SMARTc unit]
Service d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM]
Simulation & Modelling : Adaptive Response for Therapeutics in Cancer [SMARTc unit]
Service d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM]
CICCOLINI, Joseph
Simulation & Modelling : Adaptive Response for Therapeutics in Cancer [SMARTc unit]
Simulation & Modelling : Adaptive Response for Therapeutics in Cancer [SMARTc unit]
MASCAUX, Celine
Service d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM]
Service d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM]
LACARELLE, Bruno
Simulation & Modelling : Adaptive Response for Therapeutics in Cancer [SMARTc unit]
Simulation & Modelling : Adaptive Response for Therapeutics in Cancer [SMARTc unit]
BARLESI, Fabrice
Service d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM]
Service d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM]
BARBOLOSI, Dominique
Simulation & Modelling : Adaptive Response for Therapeutics in Cancer [SMARTc unit]
Simulation & Modelling : Adaptive Response for Therapeutics in Cancer [SMARTc unit]
BENZEKRY, Sébastien
Institut de Mathématiques de Bordeaux [IMB]
Modélisation Mathématique pour l'Oncologie [MONC]
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Institut de Mathématiques de Bordeaux [IMB]
Modélisation Mathématique pour l'Oncologie [MONC]
Language
en
Article de revue
This item was published in
CPT: Pharmacometrics and Systems Pharmacology. 2018p. 1-9
American Society for Clinical Pharmacology and Therapeutics ; International Society of Pharmacometrics
English Abstract
Concomitant administration of bevacizumab and pemetrexed-cisplatin is a common treatment for advanced non-squamous non-small cell lung cancer (NSCLC). Vascular normalization following bevacizumab administration may transiently ...Read more >
Concomitant administration of bevacizumab and pemetrexed-cisplatin is a common treatment for advanced non-squamous non-small cell lung cancer (NSCLC). Vascular normalization following bevacizumab administration may transiently enhance drug delivery, suggesting improved efficacy with sequential administration. To investigate optimal scheduling, we conducted a study in NSCLC-bearing mice using. First, experiments demonstrated improved efficacy when using sequential versus concomitant scheduling of bevacizumab and chemotherapy. Using a mathematical model of tumor growth under therapy accounting for the normalization effect, we predicted an optimal delay of 2.8 days between bevacizumab and chemotherapy. This prediction was confirmed experimentally, with reduced tumor growth of 38% as compared to concomitant scheduling, and prolonged survival (70 vs. 74 days). Alternate sequencing of 8 days failed in achieving similar increase in efficacy, thus emphasizing the utility of modeling support to identify optimal scheduling. The model could also be a useful tool in the clinic to personally tailor regimen sequences.Read less <
English Keywords
Drug-drug interactions
Systems biology
Population pharmacokinetics-pharmacodynamics
Pharmacokinetics-pharmacodynamics
Combination therapy
Computational biology
Mixed effect models
Personalized Therapy
Oncology
Origin
Hal imported