TPS3643 Background: No randomized studies have directly compared the role of peri-operative to adjuvant chemotherapy for resectable liver metastases. Benefit from post operative compared to peri-operative treatment has been suggested in a recent retrospective study of 499 patients with resected colorectal liver metastases which showed improved survival with entirely post-operative chemotherapy. Given this data and that of the small randomised trials demonstrating improved surgical outcomes with adjuvant chemotherapy, the role of entirely post-operative chemotherapy as a means of improving outcomes while reducing the negative effects of pre-operative treatment needs to be examined. Methods: 200 patients randomized 1:1 to 6 months of treatment post-operatively or 3 months of treatment pre-operatively and 3 months post-operatively. Site investigators will nominate chemotherapy schedule (mFOLFOX6, XELOX or FOLFIRI when adjuvant oxaliplatin received previously) prior to randomisation. Primary endpoint: proportion of patients in each arm with surgical complications within 30 days. Secondary endpoints: proportion of patients completing planned chemotherapy, post operative mortality rate (in each group), tolerability and safety of treatment, response rate by RECIST V1.1 and CEA, time to progression, time to treatment failure, overall survival, QoL (EORTC QLQ-C30 and QLQ-LMC21). A planned prospective meta-analysis with MRC (UK) and NSABP C-11 trials will have sufficient power to examine the effect of schedule (peri- or post-operative) on progression free survival (PFS). Eligibility: Patients with histologically proven colorectal cancer with radiologically confirmed, resectable liver metastases without evidence of extra-hepatic disease are eligible. Patients with synchronous metastases who have undergone resection of the primary tumour are eligible but patients requiring combined resection of primary cancer and liver metastatic disease are excluded. Patients with involved hilar nodes or wound implant metastases will not be eligible. Trial Status: Study opened to accrual August 2011.
The role of peri-operative treatment in resectable liver metastases of colorectal cancer