Cetuximab in combination with 5-fluorouracil, leucovorin and irinotecan as a neoadjuvant chemotherapy in patients with initially unresectable colorectal liver metastases

Background: The efficacy and safety of a combination of cetuximab, irinotecan, and 5-fluorouracil/leucovorin (FOLFIRI) in downsizing unresectable colorectal liver metastases was investigated. Patients and Methods: Patients with unresectable colorectal liver metastases with or without resectable extrahepatic metastasis were enrolled. 23 patients initially received 400 mg/m(2) of cetuximab, followed by a weekly infusion of 250 mg/m(2) and a biweekly dose of irinotecan (180 mg/m(2)), with 5-fluorouracil both by bolus (400 mg/m(2)) and by a 46-h infusion (total of 2,400 mg/m(2)) with leucovorin (400 mg/m(2)). Results: The overall response rate was 39.1% (n = 9; 95% confidence interval (CI): 17.6-60.7%). The most common grade 3-4 toxicities were skin reactions (30.4%) and diarrhea (26.1%). The rate of conversion to resectable liver metastases was 30.4% (n = 7; 95% CI: 10.1-50.8%). The factors found to be significantly associated with R0 resection were lower serum carcinoembryonic antigen levels after chemotherapy (p = 0.039), being chemonaive (p = 0.002), and showing a higher incidence of grade 3-4 skin toxicity (p = 0.011). Conclusions: Cetuximab with FOLFIRI may be an effective and safe treatment option for downsizing unresectable colorectal liver metastases.