Isolated Lung Perfusion as an Adjuvant Treatment of Colorectal Cancer Lung Metastases: A Preclinical Study in a Pig Model

摘要: Background The lung is a frequent site of colorectal cancer (CRC) metastases. After surgical resection, metastases recurrences have been related to the presence micrometastases, potentially accessible high dose chemotherapy administered via adjuvant isolated perfusion (ILP). We sought determine in vitro most efficient drug when CRC cell lines during short exposure and vivo its immediate delayed tolerance ILP. Methods First, efficacy various cytotoxic molecules against panel human was tested using assay after 30-minute exposure. Then, early (operative) (1 month) two concentrations molecule ILP on 19 adult pigs hemodynamic, biological histological criteria. Results In vitro, gemcitabine (GEM) selected lines. In vivo, GEM at regular (20 µg/ml) or (100 concentrations. administration associated with transient dose-dependant pulmonary vasoconstriction, leading voluntary decrease pump inflow order maintain stable artery pressure. this modulation, not any systemic leak, damage, acute toxicity. Pharmacokinetics studies revealed uptake heterogenous distribution into parenchyma, persistent cytotoxicity venous effluent. Conclusions GEM effective cells even safe reproducible technique.