The Clinical Study Of Neoadjuvant Therapy With Induction Chemotherapy,Concurrent Chemoradiotherapy,and Consolidation Chemotherapy For Locally Advanced Rectal Cancer

Objective:We design a new strategy of sandwich-like neoadjuvant treatment,integrating induction chemotherapy,5-Fu concurrent chemoradiotherapy,and consolidation chemotherapy for patients with locally advanced rectal cancer(LARC).The Objective of this study is to evaluate the efficacy and safety of this neoadjuvant treatment.Methods:This study is a prospective,single-Center,single-arm clinical trial.Patients with locally advanced rectal cancer who enrolled this study received sandwich-like neoadjuvant treatment,first with one cycle of induction chemotherapy with the XELOX regimen consisting of oxaliplatin,130 mg/m2 on day 1,with capecitabine,1250 mg/m2 twice daily for 14 days every 3 weeks,followed by chemoradiation therapy(50Gy over 5 weeks,at the same tine oral capecitabine 825mg/m2 twice daily,then with another cycle of consolidation chemotherapy with the XELOX regimen.They received the TME surgery 6 to 8 weeks after completion of radiation therapy.We received the information about each patient,include basic information,the tumor response,toxicities,surgery,pathology results and surgical complications.We use RECIST(Response Evaluation Criteria in Solid Tumors,Version 1.1)to evaluate the tumor response.Pathology results were evaluated with TRG(tumor regression grading).And toxicities were evaluated with NCICTCAE(National Cancer Institute Updates Common Terminology Criteria for Adverse Events,version 4.0).The primary endpoint of this study was rate of pathologic complete response(pCR),the secondary endpoints were toxicities related to CRT/chemotherapy,tumor regression grade,R0 resection rate and surgical complication rates.Results:From October 2014 to October 2016,38 patients were enrolled in the study.All patent completed the planned schedule of sandwich-like neoadjuvant treatment and underwent optimal surgery with total mesorectal excision(TME).During the course of neoadjuvant therapy,4 patients had grade 3 hematological toxicity events and 5 patients had grade 3 non-hematological toxicity events.Overall,1 patient developed grade 3 Neutropenia;2 patients developed grade 3 leucopenia;1 patient developed grade 3 thrombocytopenia;2 patients developed grade 3 diarrhea;1 patient developed grade 3 fatigue;and 2 patients developed grade 3 radiation dermatitis.No grade 3 or 4 toxicities were recorded for other toxicities.In this study,11 patients(28.9%)achieved pathologic complete response(pCR).According to RECIST criteria,27 patients(71.1%)achieved CR or PR.23 patients(60.5%)achieved TRG3 or TRG4.32 patients(84%)achieved T-down or N-down,19 patients(50%)achieved T-down and N-down.All patients achieved R0-resection,and 20 patients(52.6%)received a sphincter-saving procedure.Four of the 45 patients(10.5%)developed postoperative complications,including one case of anastomosis leakage,one case of anastomosis bleed,one case of ileus and one case of superficial surgical site infection.Conclusion:This strategy of sandwich-like neoadjuvant treatment,integrating induction chemotherapy,5-Fu concurrent chemoradiotherapy,and consolidation chemotherapy is effective and safe for patients with locally advanced rectal cancer.And this strategy has not increased occurrence of postoperative complications.But large randomized prospective trials are needed to determine the definite role of this sandwich-like neoadjuvant treatment.