Totally neoadjuvant chemoradiation therapy with mFOLFOX6 in locally advanced rectal cancer: A single-arm phase II study (FOTAC).

732 Background: In our previous FOWARC study, in the group of preoperative systemic chemotherapy with mFOLFOX6 combined with radiation, the pCR rate was up to 27.5%. In another study, adding mFOLFOX6 after neoadjuvant chemo radiation in locally advanced rectal cancer improve the pCR rate to 38%. This phase II study aimed to explore whether totally neoadjuvant chemoradiation therapy with mFOLFOX6 could further improve the pCR rate in locally advanced rectal cancer. Methods: Patients with fixed cT3 or cT4 rectal cancer evaluated by pelvic MRI participated in this trial. All candidates were to receive long term radiation for 25 times and 50Gy before surgery. Four cycles of mFOLFOX6 would be performed every 2 weeks during radiotherapy, and another 4-6 cycles would be added after radiotherapy and before TME. Totally, the patients will receive 6-8 cycles of chemotherapy before surgery. The primary endpoint is the pathologic complete response rate (pCR).The secondary endpoint included 3-year disease free survival rate, 3-year local recurrence rate, and safety. Results: Between April 2016 and May 2017, 81 patients were enrolled and 79 participants had received TME. Two patients required watch and wait, because the tumor location is too low to perform sphincter-preserving operation. Of 79 patients completing chemoradiotherapy and adding chemotherapy before surgery, 32.9% (26/79) of patients achieving pCR, and 54.4% (43/79) of patients had tumor downstaging to ypstage 0-I. Among patients who received 8 cycles of chemotherapy before surgery and the interval was more than 10 weeks between radiotherapy and operation, the pCR was 45.2%. Conclusions: Totally neoadjuvant chemoradiotherapy greatly improve the pCR rate and tumor downstaging rate. Clinical trial information: NCT02887313.