12. EFFECT OF CETUXIMAB ON LIVER REGENERATION AND COLORECTAL CANCER HEPATIC METASTASIS PROGRESSION IN A MURINE MODEL OF SELECTIVE PORTAL LIGATION

Abstract

Abstract Introduction The preferred treatment for patients bearing liver metastases (CRCLM) quite often includes biologic therapies such as cetuximab (anti-EGFR). The aim of this piece of work was to evaluate the effect of cetuximab as a cytoreductive agent for CRCLM in a murine model of selective portal ligation (PVL). Methods Male WAG/RijHsd rats were used in this study; thirty MHCCR-bearing animals were subjected to PVL and pretreated with cetuximab (12) or vehicle (12), and another six did not receive any treatment. In addition, another three groups of six animals were included in the study as control: untreated CRCLM-bearing animals, healthy animals subjected to PVL, healthy non-operated animals. Seven days after PVL, the percentage of remaining liver volume (%FRL) and hepatocyte nuclear area were assessed. Serum markers of hepatic, renal and systemic damage were also determined. Tumor volume was assessed by ultrasound, pre- and post-PVL. Results Liver regeneration was not substantially altered due to cetuximab treatment, attaining a %FRL between 80-90%; although the area occupied by hepatocyte nuclei was 5% smaller than in the animals of the vehicle group (43.54±9.87 vs. 45.35±9.09μm2; p<0.001). Liver function was also not altered; whereas glucose level was reduced following PVL. Cetuximab reduced tumor growth associated with post-PVL regenerative stimulation (1.12±0.45 vs. 0.53±0.16 ml; p<0.01). Conclusion These results suggest that neoadjuvant cetuximab treatment, prior to PVL, is a clinically safe option, not impairing liver regeneration, while blocking tumor progression associated with proliferative hepatic stimulus.