Optimization of sequential administration of bevacizumab plus cytotoxics in non-small cell lung cancer by combining in vivo experiments and mathematical modeling
BENZEKRY, Sébastien
Modélisation Mathématique pour l'Oncologie [MONC]
Institut de Mathématiques de Bordeaux [IMB]
Modélisation Mathématique pour l'Oncologie [MONC]
Institut de Mathématiques de Bordeaux [IMB]
BENZEKRY, Sébastien
Modélisation Mathématique pour l'Oncologie [MONC]
Institut de Mathématiques de Bordeaux [IMB]
< Reduce
Modélisation Mathématique pour l'Oncologie [MONC]
Institut de Mathématiques de Bordeaux [IMB]
Language
en
Communication dans un congrès
This item was published in
Mathematical perspectives in the biology and therapeutics of cancer, 2018-07-09, Marseille.
English Abstract
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 ...Read more >
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 that combined mathematical modeling with experimental investigations. 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.Read less <
English Keywords
Personalized oncology
Experimental therapeutics
Antiangiogenic drugs
Nonlinear mixed-effects modeling
Combinations
Origin
Hal imported