For unresectable locally advanced rectal cancer (ULARC), long-course preoperative neoadjuvant chemoradiotherapy (NACRT) was recommended by ESMO guideline. However, ULARC had the risk of not only local recurrence but also subsequent metastatic disease. In these circumstances, preoperative neoadjuvant intense chemotherapy without radiotherapy (NAC) are being investigated in multiple trials. The recent trials suggested equivalent local down staging and pCR rates of NAC using doublet therapy + bevacizumab as compared with standard NACRT. On the other hands, the addition of bevacizumab could be associated with anastomotic insufficiency or rectal perforation. Therefore, the strategy of the safe and sufficient introduction of preoperative doublet therapy + bevacizumab has been required for ULARC.
Primary end point: T down-staging rate (The rate of pT0, pTis, pT1 and pT2) Inclusion criteria: 1. Clinical stage T3 or T4, any N without distant metastases. 2. Unresectable rectal cancer by organ-sparing TME which was judged by high resolution MRI. The features include CRM < =1mm, T4b, and lateral lymph node metastasis. 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. L-OHP is 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 are assumed 1 course, and chemotherapy consisted of 4 courses. Surgery is carried out in 8 to 12 weeks after the end of chemotherapy. The type of surgery was defined by high resolution MRI after preoperative chemotherapy within 2 weeks before the date of surgery. Target sample: 32 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. The transverse loop colostomy is required before NAC in case of stenosis. 3. The diverting stoma are necessary after intestinal reconstruction.
Clinical trial identification
UMIN Clinical Trials Registry: UMIN000031626
Release date: 2018/03/08.
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.