Phase II study of neoadjuvant 5-FU plus leucovorin plus CPT-II in patients with resectable liver metastases from colorectal adenocarcinoma

Background: Following resection of liver metastases from colorectal cancer, 5-year survivals are reportedly 30-39%. It can be assumed that this clinical situation represents systemic disease. Therefore, it is postulated that systemic chemotherapy would improve outcomes, particularly in those whose disease is sensitive to the agents administered. One potential advantage of neoadjuvant chemotherapy is that it provides in vivo chemosensitivity data. Response to neoadjuvant chemotherapy could therefore guide adjuvant chemotherapy following resection of liver metastases from colorectal cancer. Methods and design: This is a prospective Phase II evaluation of outcomes in patients with potentially resectable liver metastases. Patients will receive neoadjuvant chemotherapy and will undergo resection. Postoperative chemotherapy will be directed by the degree of response to preoperative chemotherapy. All patients with Stage IV colorectal adenocarcinoma isolated to the liver that have disease that is amenable to complete ablation by resection, radiofrequency ablation, and/or cryoablation will be candidates for the trial. Patients will receive CPT-11 180 mg/m(2) IV (over 90 minutes) on day 1 with 5-FU 400 mg/m(2) bolus and 600 mg/m(2) by 22 hour infusion and calcium folinate 200 mg/m(2) on days 1 and 2, every 2 weeks. Altogether, six cycles of chemotherapy will be administered. Patients will then undergo resection and/or radiofrequency ablation. Patients who had stable disease or a clinical response with preoperative chemotherapy will receive an additional 12 cycles of CPT-11 180 mg/m(2) IV (over 90 minutes) on day 1 with 5-FU 400 mg/m2 bolus and 600 mg/m(2) by 22 hour infusion and calcium folinate 200 mg/m(2) on days 1 and 2 (given every 2 weeks). Patients with resectable disease who had progressive disease during neoadjuvant chemotherapy will receive best supportive care or an alternative agent, at the discretion of the treating physician. Those patients who are not rendered free of disease following the neoadjuvant chemotherapy and surgery will receive best supportive care or an alternative agent, at the discretion of the treating physician. The primary endpoint of the study is disease-free survival. Secondary endpoints include overall survival, safety and feasibility, response to chemotherapy, and quality of life.