Fiche publication
Date publication
janvier 2018
Journal
CPT: pharmacometrics & systems pharmacology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MASCAUX Céline
Tous les auteurs :
Imbs DC, El Cheikh R, Boyer A, Ciccolini J, Mascaux C, Lacarelle B, Barlesi F, Barbolosi D, Benzekry S
Lien Pubmed
Résumé
Concomitant administration of bevacizumab and pemetrexed-cisplatin is a common treatment for advanced nonsquamous 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. First, experiments demonstrated improved efficacy when using sequential vs. concomitant scheduling of bevacizumab and chemotherapy. Combining this data with 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 (74 vs. 70 days). Alternate sequencing of 8 days failed in achieving a 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.
Mots clés
Animals, Antineoplastic Combined Chemotherapy Protocols, administration & dosage, Bevacizumab, administration & dosage, Carcinoma, Non-Small-Cell Lung, drug therapy, Cell Line, Tumor, Cell Proliferation, drug effects, Drug Administration Schedule, Humans, Lung Neoplasms, drug therapy, Mice, Models, Theoretical, Proof of Concept Study, Xenograft Model Antitumor Assays
Référence
CPT Pharmacometrics Syst Pharmacol. 2018 01;7(1):42-50
