Introduction: 15% to 20% of patients with initially unresectable metastatic colorectal cancer (CRC) can be rendered resectable with systemic chemotherapy. The addition of anti-epidermal growth factor receptor (EGFR) therapy to systemic chemotherapy increases efficacy, theoretically increasing the number of patients with resectable liver metastasis. However the effect of anti-EGFR therapy on liver regeneration is unknown. EGFR has been shown to be activated in regenerating livers after partial hepatectomies in animal models. The purpose of our study was to determine the effect of EGFR inhibition on liver regeneration after 66% partial hepatectomy in a murine model.

Materials and methods: BALB/c mice underwent either 66% partial hepatectomy or sham laparotomy. Mice in the hepatectomy group were randomized to receive daily intraperitoneal injections of either non-specific monoclonal antibodies or monoclonal antibodies to murine EGFR; therapy was initiated the day before surgery and continued until sacrifice (days three and five). Livers were harvested, weighed, and processed for tissue analysis. Livers were examined by immunohistochemical analysis and Western blot analyses to evaluate EGFR phosphorylation, cellular proliferation, and other morphologic changes.

Results: Anti-EGFR therapy did not impair liver regeneration as assessed by liver weight on either day three or five in comparison to non-specific antibody treated controls. Immunohistochemical staining and Western blot analysis showed that EGFR levels were decreased. Hematoxylin and eosin staining showed no difference in liver morphology between the treatment groups, and proliferating cell nuclear antigen staining, likewise, showed no difference in cell proliferation between treatment groups.

Conclusion: Anti-EGFR therapy did not impair liver regeneration, hepatocyte proliferation, or liver morphology at either day three or five days after a 66% partial hepatectomy in a murine model. Our study suggests that treatment with anti-EGFR therapy during the perioperative period should not effect liver regeneration in patients undergoing partial hepatectomies.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA