Revisiting Bevacizumab + Cytotoxics Scheduling Using Mathematical Modeling: Proof of Concept Study in Experimental Non-Small Cell Lung Carcinoma.

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 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

SUBMITTER: Imbs DC 

PROVIDER: S-EPMC5784740 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature