Conversion Therapy Using mFOLFOX6 With Panitumumab for Unresectable Liver Metastases From Multiple Colorectal Cancers With Familial Adenomatous Polyposis

A 39-year-old man received a diagnosis of unresectable multiple liver metastases from multiple colorectal cancers with familial adenomatous polyposis. After construction of an ileostomy, modified FOLFOX6 (mFOLFOX6) with panitumumab was administrated because rectal cancer and sigmoid colon cancer are KRAS wild type. The 13 courses of chemotherapy resulted in a marked reduction in the size of liver metastases and sigmoid colon cancer. Consequently, curative resection with total colectomy, ileal pouch anal anastomosis, and liver metastasis resection with radiofrequency ablation was performed. Progression of KRAS wild-type rectal cancer after chemotherapy suggested that each clone from rectal and sigmoid colon cancer might have a different sensitivity to epidermal growth factor receptor antibody. Immunohistochemical analysis revealed loss of PTEN expression in rectal cancer compared with liver metastases from sigmoid colon cancer, showing that the difference of mFOLFOX6 with panitumumab might be related to activation of the PI3K-AKT pathway.Key words: Panitumumab, mFOLFOX6, Colorectal cancer, Liver metastases, Familial adenomatous polyposisThe only available treatment associated with long-term survival in patients with liver metastases from colorectal cancer is complete liver tumor resection, with 5-year survival rates ranging from 25% to 57%.¹ However, only 40% to 50% of patients with colorectal metastasis to the liver are eligible for surgical resection.² Therefore, other liver metastasis patients undergo palliative chemotherapy to stabilize the disease and prolong their overall survival.During the past decade, the biggest advance made regarding unresectable liver metastases from colorectal cancer has been the ability of oncologists to convert inoperable liver disease to resectable disease using various molecular targeting drugs.^3,4 Several clinical studies have shown that the association of chemotherapy with bevacizumab (vascular endothelial growth factor monoclonal antibody), or cetuximab epidermal growth factor receptor (EGFR) monoclonal antibody] is particularly promising in improving the resectability rate and, ultimately, survival.⁵Panitumumab is a fully human monoclonal antibody that binds specifically to the EGFR, and consequently, severe panitumumab-related infusion reactions are rare. Panitumumab, when added to FOLFOX4 (folinic acid, 5-fluorouracil, and oxaliplatin), increased response rate and improved progression-free survival in previously untreated metastatic colorectal cancer.⁶ Retrospective analyses of phase 3 trials of anti-EGFR antibodies, including cetuximab and panitumumab, found KRAS status to be an important predictive marker of efficacy, with only wild-type patients benefiting from treatment.⁷Here, we report a successful conversion therapy using modified FOLFOX6 (mFOLFOX6) plus panitumumab in a patient with familial adenomatous polyposis (FAP) who had unresectable multiple liver metastases from multiple colorectal cancers. To the best of our knowledge, we are the first researchers to demonstrate treatment of multiple target tumors derived from different clones with mFOLFOX6 and panitumumab, and to show differential panitumumab sensitivity for multiple primary tumors and liver metastases.