For resectable colorectal liver metastasis, perioperative adjuvant chemotherapy was suggested to prolong disease-free survival. However, the relapse rate was still high even after doublet therapy. To decrease the relapse rate, doublet + targetted therapy was tried but the efficacy and perioperative safety of the targetted therapy have not been significantly shown. These failures might be caused by inappropriate indication, timing of preoperative chemotherapy and short interval between chemotherapy and surgery. In these circumstances, we designed a preoperative doublet + bevacizumab therapy in high-risk patients such as synchronous liver metastasis before simultaneous resection of primary and liver metastasis.
Primary end point: Disease-free survival. Inclusion criteria: 1. Clinical any T and any N with only liver metastases. Exclusion criteria: 1. Over 75 years old. 2. The patients had thromboembolism or significant abnormal electrocardiogram or cardiovascular disease. Protocol: S-1 is administered orally at 80mg/m2/day for 14 consecutive days followed by a 7-day rest. Oxaliplatin (L-OHP) was given intravenously on days 1, at a dose of 130mg/m2/day. Bevacizumab is given intravenously on days 1, at a dose of 7.5mg/kg/day. 21 days were assumed 1 course, and chemotherapy consisted of 4 courses. Surgery was carried out 8 to 12 weeks after the end of chemotherapy. Adjuvant chemotherapy of S-1 at 80mg/m2/day for 14 consecutive days followed by a 7-day rest was initiated within 6-8 weeks after surgery. Target sample: 28 patients. Features of this trial: Paying attention to the safety and efficacy of bevacizumab compared with prior trials according to the following points; 1. Long interval between surgery and the administration of bevacizumab. 2. Preoperative chemotherapy was administered prior to resection of primary colorectal cancer in order to increase the intensity of chemotherapy. 3. The loop ostomy is required before neoadjuvant chemotherapy in case of stenosis.
Clinical trial identification
UMIN000032102, release date: 2018/04/04.
Legal entity responsible for the study
Aomori Colorectal Cancer Study (ACCS) Group.
Has not received any funding.
All authors have declared no conflicts of interest.