Southwest Oncology Group 0408: Phase II Trial of Neoadjuvant Capecitabine/Oxaliplatin/Bevacizumab for Resectable Colorectal Metastases in the Liver

Abstract

5 years, 58% are alive, but only 25%-30% have no detectable cancer.2,3 Recent studies on patients who undergo immediate resection without chemotherapy for the liver metastases report a positive margin resection rate of 11%-19%.4-6 This is clearly a great concern for patients undergoing hepatic resection because it negates the benefit of the surgical procedure and means that many of these patients might have needlessly been subjected to surgery. There are no standard recommendations for preoperative or postoperative chemotherapy, with treatment ranging from hepatic resection followed by observation, systemic chemotherapy, or combined regional hepatic arterial infusion and systemic chemotherapy. Adjuvant hepatic arterial chemotherapy with fluorodeoxyuridine plus systemic 5-fluorouracil (5-FU) with or without leucovorin might be associated with improved control of disease in the liver, but no advantage in overall or disease-free survival has been found in any study, and toxicity is significant.4 The majority of literature regarding the association of neoadjuvant and adjuvant chemotherapy with hepatic resection is retrospective, and therapy is considered without defined criteria, largely at the discretion of the treating physician. Treatment choice for adjuvant or neoadjuvant therapy has been based on data showing a survival advantage for treatment of inhomogeneous groups of patients with stage IV colon cancer who are not candidates for complete resection of disease. The rationale for this multicenter phase II study sponsored by the Southwest Oncology Group will be to prospectively assess the impact of neoadjuvant plus adjuvant chemotherapy on patients with resectable colorectal liver metastases. The primary study objective (Table 1) is to determine the proportion of patients who will undergo margin-negative liver resection (R0 resection) of hepatic colorectal metastases after neoadjuvant chemotherapy. Secondary endpoints will include assessment of tumor downstaging, overall survival, and disease-free survival; results will be compared with the extant literature.