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Revisiting bevacizumab + cytotoxics scheduling using mathematical modeling: proof of concept study in experimental non-small cell lung carcinoma

hal.structure.identifierSimulation & Modelling : Adaptive Response for Therapeutics in Cancer [SMARTc unit]
dc.contributor.authorIMBS, Diane-Charlotte
hal.structure.identifierSimulation & Modelling : Adaptive Response for Therapeutics in Cancer [SMARTc unit]
dc.contributor.authorEL CHEIKH, Raouf
hal.structure.identifierSimulation & Modelling : Adaptive Response for Therapeutics in Cancer [SMARTc unit]
hal.structure.identifierService d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM]
dc.contributor.authorBOYER, Arnaud
hal.structure.identifierSimulation & Modelling : Adaptive Response for Therapeutics in Cancer [SMARTc unit]
dc.contributor.authorCICCOLINI, Joseph
hal.structure.identifierService d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM]
dc.contributor.authorMASCAUX, Celine
hal.structure.identifierSimulation & Modelling : Adaptive Response for Therapeutics in Cancer [SMARTc unit]
dc.contributor.authorLACARELLE, Bruno
hal.structure.identifierService d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM]
dc.contributor.authorBARLESI, Fabrice
hal.structure.identifierSimulation & Modelling : Adaptive Response for Therapeutics in Cancer [SMARTc unit]
dc.contributor.authorBARBOLOSI, Dominique
hal.structure.identifierInstitut de Mathématiques de Bordeaux [IMB]
hal.structure.identifierModélisation Mathématique pour l'Oncologie [MONC]
dc.contributor.authorBENZEKRY, Sébastien
dc.date.accessioned2024-04-04T03:07:43Z
dc.date.available2024-04-04T03:07:43Z
dc.date.issued2018
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/193469
dc.description.abstractEnConcomitant 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.
dc.language.isoen
dc.publisherAmerican Society for Clinical Pharmacology and Therapeutics ; International Society of Pharmacometrics
dc.subject.enDrug-drug interactions
dc.subject.enSystems biology
dc.subject.enPopulation pharmacokinetics-pharmacodynamics
dc.subject.enPharmacokinetics-pharmacodynamics
dc.subject.enCombination therapy
dc.subject.enComputational biology
dc.subject.enMixed effect models
dc.subject.enPersonalized Therapy
dc.subject.enOncology
dc.title.enRevisiting bevacizumab + cytotoxics scheduling using mathematical modeling: proof of concept study in experimental non-small cell lung carcinoma
dc.typeArticle de revue
dc.identifier.doi10.1002/psp4.12265
dc.subject.halSciences du Vivant [q-bio]/Cancer
dc.subject.halMathématiques [math]/Systèmes dynamiques [math.DS]
dc.subject.halSciences du Vivant [q-bio]/Bio-Informatique, Biologie Systémique [q-bio.QM]
dc.subject.halSciences du Vivant [q-bio]/Sciences pharmaceutiques/Pharmacologie
bordeaux.journalCPT: Pharmacometrics and Systems Pharmacology
bordeaux.page1-9
bordeaux.hal.laboratoriesInstitut de Mathématiques de Bordeaux (IMB) - UMR 5251*
bordeaux.institutionUniversité de Bordeaux
bordeaux.institutionBordeaux INP
bordeaux.institutionCNRS
bordeaux.peerReviewedoui
hal.identifierhal-01624423
hal.version1
hal.popularnon
hal.audienceInternationale
hal.origin.linkhttps://hal.archives-ouvertes.fr//hal-01624423v1
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=CPT:%20Pharmacometrics%20and%20Systems%20Pharmacology&rft.date=2018&rft.spage=1-9&rft.epage=1-9&rft.au=IMBS,%20Diane-Charlotte&EL%20CHEIKH,%20Raouf&BOYER,%20Arnaud&CICCOLINI,%20Joseph&MASCAUX,%20Celine&rft.genre=article


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