Combination of tumor cell anti-adhesion and anti-tumor effect to prevent recurrence after cytoreductive surgery in a mice model

Abstract

One of the main problems of colorectal cancer is not the treatment of the primary tumor but the metastatic stage. Means of metastatic spread is the invasion of the peritoneal cavity which leads to peritoneal metastasis (PM). PM cannot be easily cured, and the current treatments is rather heavy, combining cytoreductive surgery with intravenous and intraperitoneal chemotherapy. This therapeutic procedure is associated with significant morbidity, altered patient quality of life and poor prognosis. We postulated that development of a prophylactic treatment could be of high interest in this context. In this study, we formulated an anti-adhesive thermogel which contains chemotherapeutics to play a role of a barrier against tumor cells implantation, avoiding their adhesion and treating the remaining tumor cells with chemotherapy intraperitoneally in a mice model of PM. The bioavailability of the thermogel was tested intraperitoneally in mice. No sign of toxicity was observed in terms of change in body weight, anatomopathology and blood biomarkers. In vitro experiments proved that the thermogel induced limited adhesion of the tumor cells. Loading of oxaliplatin (Ox) and 5-Fluorouracil (5-FU) into the thermogel were able to significantly decreased peritoneal carcinomatosis index (PCI) (−58%) and ascites (−70%) in a murine model of peritoneal metastases. These pre-clinical results confirmed that smart thermogel associated with standard chemotherapy 5-FU and Ox could be a good candidate to decrease the risk of tumor cell implantation during cytoreductive surgery and prevent future metastatic process.